1,393 results on '"*CENTRAL nervous system physiology"'
Search Results
2. Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease.
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White, Abigail G., Elias, Elias, Orozco, Andrea, Robinson, Shivon A., and Manners, Melissa T.
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TUMOR necrosis factors , *PSYCHOLOGICAL stress , *PERIPHERAL nervous system , *NEUROINFLAMMATION , *ALTERNATIVE medicine , *CENTRAL nervous system physiology - Abstract
The brain is the central organ of adaptation to stress because it perceives and determines threats that induce behavioral, physiological, and molecular responses. In humans, chronic stress manifests as an enduring consistent feeling of pressure and being overwhelmed for an extended duration. This can result in a persistent proinflammatory response in the peripheral and central nervous system (CNS), resulting in cellular, physiological, and behavioral effects. Compounding stressors may increase the risk of chronic-stress-induced inflammation, which can yield serious health consequences, including mental health disorders. This review summarizes the current knowledge surrounding the neuroinflammatory response in rodent models of chronic stress—a relationship that is continually being defined. Many studies investigating the effects of chronic stress on neuroinflammation in rodent models have identified significant changes in inflammatory modulators, including nuclear factor-κB (NF-κB) and toll-like receptors (TLRs), and cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6. This suggests that these are key inflammatory factors in the chronic stress response, which may contribute to the establishment of anxiety and depression-like symptoms. The behavioral and neurological effects of modulating inflammatory factors through gene knockdown (KD) and knockout (KO), and conventional and alternative medicine approaches, are discussed. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Temperament Affected Visuospatial Orienting on Discrimination Tasks.
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Bielas, Jacek, Przybycień, Damian, and Michalczyk, Łukasz
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CENTRAL nervous system physiology , *TEMPERAMENT , *TASK performance , *PROMPTS (Psychology) , *BEHAVIOR , *DESCRIPTIVE statistics , *PSYCHOLOGY , *SPACE perception , *VISUAL perception - Abstract
In the Posner cueing paradigm, the early attentional capture and subsequent inhibition of return (IOR) of attention to the same location, although they are microscale phenomena measured in milliseconds, seem to encapsulate the interaction between two fundamental dimensions of behavior - engaging in and sustaining activity versus withdrawing from and inhibiting activity. In the field of differential psychology, the dynamics of reciprocal relations between these behavioral dimensions have been thought to be determined by central nervous system properties that constitute an individual's temperament. Yet the research on any differential effects of temperament on visuospatial orienting is rather sparse and has produced ambiguous results. Here, we used saccadic responses to measure whether individual differences in reactivity as a temperamental trait might affect orienting of visuospatial attention on discrimination cueing tasks. Our results suggested that, in individuals with lower reactivity, attentional capture took place at a short stimulus onset asynchrony (SOA), producing a facilitatory cueing effect, which was not the case in those who were higher in reactivity. We explain and discuss these results with the Regulative Theory of Temperament. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Safety of Anti-Reelin Therapeutic Approaches for Chronic Inflammatory Diseases.
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Calvier, Laurent, Alexander, Anna, Marckx, Austin T., Kounnas, Maria Z., Durakoglugil, Murat, and Herz, Joachim
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THERAPEUTICS , *WESTERN diet , *NEUROPLASTICITY , *CHRONIC diseases , *CENTRAL nervous system , *CARDIOVASCULAR system , *CENTRAL nervous system physiology - Abstract
Reelin, a large extracellular glycoprotein, plays critical roles in neuronal development and synaptic plasticity in the central nervous system (CNS). Recent studies have revealed non-neuronal functions of plasma Reelin in inflammation by promoting endothelial–leukocyte adhesion through its canonical pathway in endothelial cells (via ApoER2 acting on NF-κB), as well as in vascular tone regulation and thrombosis. In this study, we have investigated the safety and efficacy of selectively depleting plasma Reelin as a potential therapeutic strategy for chronic inflammatory diseases. We found that Reelin expression remains stable throughout adulthood and that peripheral anti-Reelin antibody treatment with CR-50 efficiently depletes plasma Reelin without affecting its levels or functionality within the CNS. Notably, this approach preserves essential neuronal functions and synaptic plasticity. Furthermore, in mice induced with experimental autoimmune encephalomyelitis (EAE), selective modulation of endothelial responses by anti-Reelin antibodies reduces pathological leukocyte infiltration without completely abolishing diapedesis. Finally, long-term Reelin depletion under metabolic stress induced by a Western diet did not negatively impact the heart, kidney, or liver, suggesting a favorable safety profile. These findings underscore the promising role of peripheral anti-Reelin therapeutic strategies for autoimmune diseases and conditions where endothelial function is compromised, offering a novel approach that may avoid the immunosuppressive side effects associated with conventional anti-inflammatory therapies. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Dopamine and noradrenaline activate spinal astrocyte endfeet via D1‐like receptors.
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Montalant, Alexia, Kiehn, Ole, and Perrier, Jean‐François
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DOPAMINE , *CENTRAL nervous system physiology , *DOPAMINE antagonists , *NORADRENALINE , *INTRACELLULAR calcium , *NEUROTRANSMITTER receptors , *CENTRAL nervous system - Abstract
Astrocytes, the most abundant glial cells in the central nervous system, respond to a wide variety of neurotransmitters binding to metabotropic receptors. Here, we investigated the intracellular calcium responses of spinal cord astrocytes to dopamine and noradrenaline, two catecholamines released by specific descending pathways. In a slice preparation from the spinal cord of neonatal mice, puff application of dopamine resulted in intracellular calcium responses that remained in the endfeet. Noradrenaline induced stronger responses that also started in the endfeet but spread to neighbouring compartments. The intracellular calcium responses were unaffected by blocking neuronal activity or inhibiting various neurotransmitter receptors, suggesting a direct effect of dopamine and noradrenaline on astrocytes. The intracellular calcium responses induced by noradrenaline and dopamine were inhibited by the D1 receptor antagonist SCH 23390. We assessed the functional consequences of these astrocytic responses by examining changes in arteriole diameter. Puff application of dopamine or noradrenaline resulted in vasoconstriction of spinal arterioles. However, blocking D1 receptors or manipulating astrocytic intracellular calcium levels did not abolish the vasoconstrictions, indicating that the observed intracellular calcium responses in astrocyte endfeet were not responsible for the vascular changes. Our findings demonstrate a compartmentalized response of spinal cord astrocytes to catecholamines and expand our understanding of astrocyte–neurotransmitter interactions and their potential roles in the physiology of the central nervous system. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Implications of Inflammatory Processes on a Developing Central Nervous System in Childhood‐Onset Systemic Lupus Erythematosus.
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van der Heijden, Hanne, Rameh, Vanessa, Golden, Emma, Ronen, Itamar, Sundel, Robert P., Knight, Andrea, Chang, Joyce C., and Upadhyay, Jaymin
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CENTRAL nervous system physiology , *COGNITION disorder risk factors , *ISCHEMIA , *STUDENT health , *BLOOD-brain barrier , *INFLAMMATION , *CHILD development , *SELF-management (Psychology) , *MENTAL health , *MAGNETIC resonance imaging , *NEURAL development , *RISK assessment , *NEUROLOGIC manifestations of general diseases , *AGE factors in disease , *QUALITY of life , *AFFECTIVE disorders , *SYSTEMIC lupus erythematosus , *NEURORADIOLOGY , *DISEASE risk factors , *DISEASE complications , *CHILDREN - Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is increasingly affecting pediatric and adult populations. Neuropsychiatric manifestations (ie, cognitive dysfunction and mood disorders) appear to occur with greater severity and poorer prognosis in childhood‐onset SLE (cSLE) versus adult‐onset SLE, negatively impacting school function, self‐management, and psychosocial health, as well as lifelong health‐related quality of life. In this review, we describe pathogenic mechanisms active in cSLE, such as maladaptive inflammatory processes and ischemia, which are hypothesized to underpin central phenotypes in patients with cSLE, and the role of alterations in protective central nervous system (CNS) barriers (ie, the blood–brain barrier) are also discussed. Recent findings derived from novel neuroimaging approaches are highlighted because the methods employed in these studies hold potential for identifying CNS abnormalities that would otherwise remain undetected with conventional multiple resonance imaging studies (eg, T2‐weighted or fluid‐attenuated inversion recovery sequences). Furthermore, we propose that a more robust presentation of neuropsychiatric symptoms in cSLE is in part due to the harmful impact of a chronic inflammatory insult on a developing CNS. Although the immature status of the CNS may leave patients with cSLE more vulnerable to harboring neuropsychiatric manifestations, the same property may represent a greater urgency to reverse the maladaptive effects associated with a proneuroinflammatory state, provided that effective diagnostic tools and treatment strategies are available. Finally, considering the crosstalk among the CNS and other organ systems affected in cSLE, we postulate that a finer understanding of this interconnectivity and its role in the clinical presentation in cSLE is warranted. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Neuroimmune regulation in the pancreas.
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Xiaofan Ding, Jianhui Chen, and Wenwen Zeng
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PANCREATIC diseases , *ENTERIC nervous system , *IMMUNE response , *DIABETES , *CENTRAL nervous system physiology - Abstract
The pancreas exerts endocrine and exocrine functions in energy balance. The neural innervation and immune milieu are both crucial in supporting pancreatic homeostasis. The neuronal network connects the pancreas with the central nervous system (CNS) and the enteric nervous system (ENS) and sustains metabolic activities. The nerves in the pancreas are categorized as spinal sensory afferent fibers, vagal sensory afferent nerves, autonomic fibers of both sympathetic and parasympathetic divisions, and fibers from the ENS and intrapancreatic ganglia. They innervate different regions and various cell types, which collectively determine physiological functions. Studies have established that the diverse pathological conditions, including pancreatitis, diabetes, and pancreatic tumor, are attributed to aberrant immune reactions; however, it is largely not clear how the neuronal network may influence the disease conditions. Enlightened by the recent advances illuminating the organ-wide neuronal architecture and the dysfunctions in pancreatic disorders, this review will highlight emerging opportunities to explore the cellular interrelationship, particularly the neuroimmune components in pancreatic health and diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Fibroblasts: New players in the central nervous system?
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Lihui Duan and Xiang Yu
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FIBROBLASTS , *CENTRAL nervous system physiology , *EXTRACELLULAR matrix , *AGING , *RNA sequencing - Abstract
Fibroblasts are typically described as cells that produce extracellular matrix, contribute to the formation of connective tissue, and maintain the structural framework of tissues. Fibroblasts are the first cell type to be transdifferentiated into inducible pluripotent stem cells (iPSCs), demonstrating their versatility and reprogrammability. Currently, there is relatively extensive characterization of the anatomical, molecular, and functional diversity of fibroblasts in different peripheral organs and tissues. With recent advances in single cell RNA sequencing, heterogeneity and diversity of fibroblasts in the central nervous system (CNS) have also begun to emerge. Based on their distinct anatomical locations in the meninges, perivascular space, and choroid plexus, as well as their molecular diversity, important roles for fibroblasts in the CNS have been proposed. Here, we draw inspirations from what is known about fibroblasts in peripheral tissues, in combination with their currently identified CNS locations and molecular characterizations, to propose potential functions of CNS fibroblasts in health and disease. Future studies, using a combination of technologies, will be needed to determine the bona fide in vivo functions of fibroblasts in the CNS. [ABSTRACT FROM AUTHOR]
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- 2024
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9. The nervous system and associated disorders.
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Teixeira, Luis
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ALZHEIMER'S disease treatment , *TREATMENT of epilepsy , *STROKE treatment , *CENTRAL nervous system physiology , *STROKE diagnosis , *MENINGITIS treatment , *DIAGNOSIS of epilepsy , *NEURAL physiology , *ALZHEIMER'S disease diagnosis , *MIGRAINE diagnosis , *MENINGITIS diagnosis , *OCCUPATIONAL roles , *NEUROLOGICAL disorders , *STROKE , *ALZHEIMER'S disease , *NURSING care plans , *MIGRAINE , *EPILEPSY , *NURSES , *MENINGITIS , *NEUROGLIA , *MEDICAL needs assessment , *NURSING assessment - Abstract
Disorders of the nervous system, encompassing the brain, spinal cord and peripheral nerves, have emerged as a significant public health issue, with profound implications for individuals worldwide. These conditions result in significant morbidity and mortality. Many patients with neurological disorders often have comorbidities, further complicating their clinical presentation. Therefore, nurses must possess a comprehensive understanding of the nervous system and its associated disorders to formulate detailed care plans that address the unique needs of each patient. This article aims to explore the underlying pathophysiology of some of the most prevalent neurological disorders and how this informs effective patient assessment and diagnostic strategies. A further article will build on this to consider patient assessment and formulating a care plan in more detail. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Does manual therapy meaningfully change quantitative sensory testing and patient reported outcome measures in patients with musculoskeletal impairments related to the spine?: A 'trustworthy' systematic review and meta-analysis.
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Riley, Sean P., Swanson, Brian T., Shaffer, Stephen M., Flowers, Daniel W., Hofbauer, Margaret A., and Liebano, Richard E.
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CENTRAL nervous system physiology , *MUSCULOSKELETAL system diseases , *CINAHL database , *ONLINE information services , *MEDICAL databases , *SPINE diseases , *META-analysis , *SYSTEMATIC reviews , *PHYSICAL therapy , *HEALTH outcome assessment , *PAIN threshold , *TREATMENT effectiveness , *MANIPULATION therapy , *MUSCULOSKELETAL pain , *MEDLINE , *ADULTS - Abstract
To perform a 'trustworthy' systematic review (SR) with meta-analysis on the potential mechanisms of manual therapy used to treat spinal impairments. SR with meta-analysis Articles published between January 2010 and October 2022 from CENTRAL, CINAHL, MEDLINE, PubMed, ProQuest, and PEDro. This SR included English-language randomized clinical trials (RCTs) involving manual therapy to treat spinal impairments in adults. The primary outcome was pressure pain thresholds (PPTs). To synthesize RCTs with high confidence in estimated effects using the GRADE, RCTs with questionable prospective, external, and internal validity, and high risk of bias (RoB) were excluded. Following title and abstract screening, 89 full-text RCTs were reviewed. Twenty-two studies included the criteria of interest. Sixteen were not prospectively registered, two contained discussion/conclusions judged to be inconsistent with the registry, and one was rated as having a high RoB. Three studies met the inclusion criteria; heterogeneous interventions and locations for PPT testing prevented synthesis into practice recommendations. The two studies with high confidence in estimated effects had small effect sizes, and one study had confidence intervals that crossed zero for the outcome measures of interest. Standardized PPT testing, as a potential measure of centrally mediated pain, could provide clues regarding the mechanisms of manual therapy or help identify/refine research questions. High-quality RCTs could not be synthesized into strong conclusions secondary to the dissimilarity in research designs. Future research regarding quantitative sensory testing should develop RCTs with high confidence in estimated effects that can be translated into strong recommendations. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Clinical features of chronic primary pain in individuals presenting painful temporomandibular disorder and comorbidities.
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dos Santos Proença, Juliana, Baad‐Hansen, Lene, do Vale Braido, Guilherme Vinícius, Campi, Letícia Bueno, and de Godoi Gonçalves, Daniela Aparecida
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CENTRAL nervous system physiology , *DIAGNOSIS of mental depression , *CHRONIC pain , *SLEEP quality , *PAIN measurement , *CROSS-sectional method , *ONE-way analysis of variance , *FIBROMYALGIA , *RESEARCH funding , *QUESTIONNAIRES , *CHI-squared test , *ANALYSIS of covariance , *TEMPOROMANDIBULAR disorders , *PSYCHOPHYSIOLOGY , *ANXIETY , *COMORBIDITY , *PRIMARY headache disorders , *SYMPTOMS , *DISEASE complications - Abstract
Background: The diagnosis of chronic primary pain (CPP), according to the recently released International Classification of Disease (ICD‐11) criteria, refers to conditions with complex aetiologies. CPP is characterized by specific clinical features such as generalized sensory hypersensitivity and widespread pain, and is associated with functional disability and emotional distress. Objective: This study investigated clinical features of CPP in individuals with painful temporomandibular disorders (TMD) and comorbidities (fibromyalgia, migraine and/or tension‐type headache). Methods: This cross‐sectional study was conducted with a sample of 129 individuals. Painful TMD, fibromyalgia and primary headaches were evaluated based on well‐established international criteria. Generalized sensory hypersensitivity was assessed using psychophysical tests. Symptoms of anxiety and depression were assessed by the Generalized Anxiety Disorder‐7 and Patient Health Questionnaire‐9. The Central Sensitization Inventory was applied to assess central sensitization‐related symptoms and the Pittsburg Sleep Quality Index to evaluate the quality of sleep. The presence of widespread pain was assessed using a body map. The sample was stratified into three groups: control (n = 25), TMD—painful TMD only (n = 35) and TMD + Cm—painful TMD and comorbidities (n = 69). Statistical analysis was performed using one‐way ANOVA, chi‐squared test and ANCOVA, considering gender as a covariate (α =.05). Results: Compared to controls, individuals presenting painful TMD and comorbidities showed lower pressure pain thresholds in all evaluated areas (p ≤.012) and a higher number of painful areas in the body (p =.001). They presented more symptoms of anxiety (p =.040) and depression (p =.018), and a higher score in the Central Sensitization Inventory (p ≤.006) than the other groups. Conclusion: Individuals with painful TMD and comorbidities presented more clinical features of CPP compared to those affected by TMD only. [ABSTRACT FROM AUTHOR]
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- 2024
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12. American College of Toxicology.
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WEIGHT loss , *DOPAMINE receptors , *CENTRAL nervous system physiology , *MONOCLONAL antibodies , *ANIMAL tracks , *FETAL brain , *LYSOSOMES , *HEALTH facilities - Abstract
This document is a collection of abstracts from the 44th Annual Meeting of the American College of Toxicology, covering a range of topics related to toxicology research. The abstracts discuss various studies, including the protective effect of an antioxidant on kidney fibrosis in mice, sex differences in the lung-brain axis transcriptome in response to exposure to indoor fungi, and the evaluation of respiratory sensitizers using an in vitro model. Other studies explore the role of asparagine synthetase in colorectal cancer tumor metabolism, the induction of platinum resistance in ovarian cancer by certain substances, and the modulation of lung injury and inflammation by an RNA-binding protein. Additionally, the frequency of potential drug interactions in pediatric patients and the rescue role of myricetin in testicular oxidative stress, inflammation, and apoptosis in a rat model of Parkinson's disease are examined. The document also includes studies on the effects of nicotine products on gingival tissue, the safety evaluation of a novel sweetener alternative, the cardiovascular effects of a specific drug in monkeys, the use of an in silico system for drug development assessments, the release of cardiac troponin I from cardiomyocytes, the Membrane Proteome Array platform for assessing biotherapeutics, the translational and in silico assessment of liver injury for a specific compound, a modified method for collecting cerebrospinal fluid in rodents and monkeys, and different methods of delivering gene therapies to the central nervous system in non-human primates. These abstracts provide [Extracted from the article]
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- 2024
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13. Cut homeodomain transcription factor is a novel regulator of growth and morphogenesis of cortex glia niche around neural cells.
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Yadav, Vaishali, Mishra, Ramkrishna, Das, Papri, and Arya, Richa
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CENTRAL nervous system physiology , *NEURAL physiology , *STEM cells , *RESEARCH funding , *DESCRIPTIVE statistics , *GENOTYPES , *INSECTS , *TRANSCRIPTION factors , *DATA analysis software , *BIOLOGICAL assay - Abstract
Cortex glia in Drosophila central nervous system form a niche around neural cells for necessary signals to establish cross talk with their surroundings. These cells grow and expand their thin processes around neural cell bodies. Although essential for the development and function of the nervous system, how these cells make extensive and intricate connected networks remains largely unknown. In this study, we show that Cut, a homeodomain transcription factor, directly regulates the fate of the cortex glia, impacting neural stem cell (NSC) homeostasis. Focusing on the thoracic ventral nerve cord, we found that Cut is required for the normal growth and development of cortex glia and timely increase in DNA content through endocycle to later divide via acytokinetic mitosis. Knockdown of Cut in cortex glia significantly reduces the growth of cellular processes, the network around NSCs, and their progeny's cell bodies. Conversely, overexpression of Cut induces overall growth of the main processes at the expense of side ones. Whereas the Cut knockdown slows down the timely increase of DNA, the Cut overexpression results in a significant increase in nuclear size and volume and a 3-fold increase in DNA content of cortex glia. Further, we note that constitutively high Cut also interfered with nuclei separation during acytokinetic mitosis. Since the cortex glia form syncytial networks around neural cells, the finding identifies Cut as a novel regulator of glial growth and variant cell cycles to support a functional nervous system. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Effects of sleep quality on pain, cognitive factors, central sensitization, and quality of life in patients with chronic low back pain.
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Moriki, Kento, Ogihara, Hirofumi, Yoshikawa, Koji, Kikuchi, Kenta, Endo, Ryunosuke, and Sato, Takaaki
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CENTRAL nervous system physiology , *CHRONIC pain , *LUMBAR pain , *SLEEP quality , *STRUCTURAL equation modeling , *CROSS-sectional method , *HEALTH outcome assessment , *COMPARATIVE studies , *QUALITY of life , *ATTRIBUTION (Social psychology) , *QUESTIONNAIRES , *COGNITIVE testing - Abstract
BACKGROUND: Sleep quality in patients with chronic low back pain (CLBP) may affect quality of life (QoL), possibly due to worsening pain, central sensitization (CS), and cognitive factors. However, causal relationship among the factors has not been confirmed yet. OBJECTIVE: The purpose of this study was to test the hypothesis that sleep quality in patients with CLBP is attributable to pain, cognitive factors, and CS, and influences QoL, by structural covariance analysis. METHODS: This is a cross-sectional study. Participants were recruited from six health care facilities and 101 patients with CLBP were included. Structural covariance analysis assessed the fit of data to the model using goodness of fit index (GFI), adjusted goodness of fit index (AGFI), comparative fit index (CFI), and mean squared approximation error (RMSEA). RESULTS: The structural covariance analysis showed that the goodness-of-fit indices were high (GFI = 0.993, AGFI = 0.964, CFI = 1.00, RMSEA < 0.01). Sleep quality was not directly influenced by QoL but rather by CS and cognitive factors. CONCLUSION: This study suggests that sleep quality in patients with CLBP is indirectly mediated through multiple pathways, including cognitive factors and CS, which may influence QoL. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Anesthetic Management of Patients Undergoing Electroconvulsive Therapy.
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Sebastian, Sydna
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MENTAL illness treatment , *CENTRAL nervous system physiology , *ELECTRODES , *PROPOFOL , *DEEP brain stimulation , *COCHLEAR implants , *ANESTHESIA , *GENERAL anesthesia , *CARDIOVASCULAR system physiology , *MUSCLE relaxants , *ELECTROCONVULSIVE therapy , *ANESTHETICS , *AIRWAY (Anatomy) , *CONTINUING education units , *GLYCOPYRROLATE , *IMPLANTABLE cardioverter-defibrillators , *ARTIFICIAL respiration , *INFORMED consent (Medical law) , *AFFECTIVE disorders , *MENTAL depression , *DECISION making , *KETAMINE , *ETOMIDATE , *REMIFENTANIL , *PATIENT education , *CARDIAC pacemakers , *BARBITURATES , *MEDICAL needs assessment - Abstract
Electroconvulsive Therapy (ECT) is an effective treatment for mood disorders, particularly treatment-resistant depression, and several psychiatric illnesses. Anesthetic management of patients undergoing ECT requires an understanding of ECT, the physiologic changes induced by electrical stimulus, the anesthetic agents used, and the potential complications associated with the procedure. Numerous medical and surgical conditions can impact procedural approach and anesthetic management. ECT is challenging due to its typically off-site location, fast-paced general anesthesia with bag-mask ventilation, selection of anesthetic agents that minimally affect the seizure, patient's comorbidities, and unique physiologic responses. This comprehensive review aims to update anesthetists on the periprocedural management of patients undergoing ECT. [ABSTRACT FROM AUTHOR]
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- 2023
16. Neural correlates of central pain sensitization in chronic low back pain: a resting-state fMRI study.
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Fan, NingJian, Chen, JiXi, Zhao, Bing, Liu, LiYun, Yang, WeiZhen, Chen, Xian, Lu, ZhanBin, Wang, LiGong, Cao, HengCong, and Ma, AiGuo
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CENTRAL nervous system physiology , *CHRONIC pain , *LUMBAR pain , *PAIN measurement , *MAGNETIC resonance imaging , *CASE-control method , *PEARSON correlation (Statistics) , *PAIN threshold , *FACTOR analysis , *ATTENTION , *RESEARCH funding , *PAIN catastrophizing , *DEFAULT mode network - Abstract
Purpose: The objective of this study is to explore the neural correlates of pain sensitization in patients with chronic low back pain (cLBP). While the association between cLBP and pain sensitization has been widely reported, the underlying brain mechanism responsible for this relationship requires further investigation. Methods: Our study included 56 cLBP patients and 56 healthy controls (HC). Functional magnetic resonance imaging data were obtained, and the voxel-wise amplitude of low-frequency fluctuation (ALFF) was calculated to identify brain alterations in cLBP patients compared to HC groups. Pearson correlation coefficients were computed to explore the association between clinical data and brain alterations. Furthermore, mediation analyses were performed to investigate the path association between brain alterations and pain-related behaviors. Results: Our findings revealed that patients with cLBP exhibited higher sensitivity, attention, and catastrophizing tendencies towards pain compared to HC. Furthermore, cLBP patients displayed significantly higher ALFF in various brain regions within the "pain matrix" and the default mode network when compared to HC. The altered precuneus ALFF was positively correlated with pain intensity (R = 0.51, P<0.001) and was negatively correlated with pain sensitivity (R = −0.43, P<0.001) in cLBP patients. Importantly, the effect of altered precuneus ALFF on pain intensity was mediated by pain threshold in these patients. Conclusion: Our study suggests that altered neural activity in the precuneus may contribute to pain hypersensitivity, which further exacerbating pain in cLBP patients. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Effects of Orthopedic Manual Therapy on Pain Sensitization in Patients With Chronic Musculoskeletal Pain.
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Martínez-Pozas, Oliver, Sánchez-Romero, Eleuterio A., Beltran-Alacreu, Héctor, Arribas-Romano, Alberto, Cuenca-Martínez, Ferran, Villafañe, Jorge Hugo, and Fernández-Carnero, Josué
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CHRONIC pain treatment , *CENTRAL nervous system physiology , *ONLINE information services , *CINAHL database , *MEDICAL databases , *META-analysis , *CONFIDENCE intervals , *PAIN measurement , *MEDICAL information storage & retrieval systems , *SYSTEMATIC reviews , *SOCIAL services case management , *TREATMENT effectiveness , *MANIPULATION therapy , *MUSCULOSKELETAL pain , *QUALITY of life , *DESCRIPTIVE statistics , *VOCATIONAL rehabilitation , *MEDLINE , *DATA analysis software , *HYPERALGESIA - Abstract
Objective: The aim of this umbrella review with meta-meta-analysis was to assess the effectiveness of orthopedic manual therapy in isolation on pain sensitization in patients with chronic musculoskeletal pain. Design: A systematic search was performed in different databases including systematic reviews with or without meta-analysis. The outcome measures included were pressure pain threshold, temporal summation, and conditioned pain modulation. The results of the different reviews were statistically synthesized through a random-effect meta-analysis, of all standardized mean differences and the corresponding 95% confidence interval reported by each study. Results: For mechanical hyperalgesia, the meta-meta-analysis of three meta-analyses revealed a statistically significant small-moderate effect of orthopedic manual therapy, with no evidence of heterogeneity and moderate-quality evidence. In terms of temporal summation, one meta-analysis revealed a statistically significant small effect of orthopedic manual therapy intervention, with moderate heterogeneity and low quality of evidence. Finally, one review without meta-analysis found that orthopedic manual therapy improved endogenous analgesia with low-quality evidence. Conclusion: Orthopedic manual therapy in isolation improved mechanical hyperalgesia with moderate-quality evidence, as well as temporal summation and conditioned pain modulation with low-quality evidence. However, its effects are limited only to immediate and short-term. [ABSTRACT FROM AUTHOR]
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- 2023
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18. INPP5D /SHIP1: Expression, Regulation and Roles in Alzheimer's Disease Pathophysiology.
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Olufunmilayo, Edward O. and Holsinger, R. M. Damian
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ALZHEIMER'S disease , *HOMEOSTASIS , *DISEASE risk factors , *GENOTYPE-environment interaction , *PATHOLOGICAL physiology , *GENETIC variation , *CENTRAL nervous system physiology - Abstract
Alzheimer's disease (AD) is the most common form of dementia, accounting for approximately 38.5 million cases of all-cause dementia. Over 60% of these individuals live in low- and middle-income countries and are the worst affected, especially by its deleterious effects on the productivity of both patients and caregivers. Numerous risk factors for the disease have been identified and our understanding of gene–environment interactions have shed light on several gene variants that contribute to the most common, sporadic form of AD. Microglial cells, the innate immune cells of the central nervous system (CNS), have long been established as guardians of the brain by providing neuroprotection and maintaining cellular homeostasis. A protein with a myriad of effects on various important signaling pathways that is expressed in microglia is the Src Homology 2 (SH2) domain-containing Inositol 5′ Phosphatase 1 (SHIP1) protein. Encoded by the INPP5D (Inositol Polyphosphate-5-Phosphatase D) gene, SHIP1 has diminutive effects on most microglia signaling processes. Polymorphisms of the INPP5D gene have been found to be associated with a significantly increased risk of AD. Several studies have elucidated mechanistic processes by which SHIP1 exerts its perturbations on signaling processes in peripheral immune cells. However, current knowledge of the controllers of INPP5D/SHIP1 expression and the idiosyncrasies of its influences on signaling processes in microglia and their relevance to AD pathophysiology is limited. In this review, we summarize these discoveries and discuss the potential of leveraging INPP5D/SHIP1 as a therapeutic target for Alzheimer's disease. [ABSTRACT FROM AUTHOR]
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- 2023
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19. Parathyroid adenoma in children: A rare cause of primary hyperparathyroidism.
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Roy, Srotaswini, Agrawal, Poorvi, Wade, Poonam, and Bhagwat, Nikhil
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HYPERPARATHYROIDISM , *HYPERCALCEMIA , *CENTRAL nervous system physiology , *PERIOPERATIVE care , *CLINICAL trials - Abstract
Primary hyperparathyroidism (PHPT) is rare in children. The most common cause of PHPT is parathyroid adenoma, which occurs either sporadically or as part of the syndrome (the most common being multiple endocrine neoplasia syndrome). The clinical presentation is often vague with nonspecific symptoms involving the gastrointestinal, renal, musculoskeletal, and central nervous systems making the diagnosis challenging. Biochemical profiles and modern imaging techniques are the mainstay for diagnosing the condition, planning the right treatment, and for perioperative management. Herein, we present a case of PHPT who presented to us with all the classical symptoms of hypercalcemia described as "Bones, Stones, Groans, and Moans." [ABSTRACT FROM AUTHOR]
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- 2024
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20. People with multiple sclerosis and unilateral peripheral vestibular loss demonstrate similar alterations in head and trunk turning kinematics compared to healthy controls.
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Weston, Angela R., Dibble, Leland E., Hoppes, Carrie W., and Loyd, Brian J.
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GAIT in humans , *MULTIPLE sclerosis , *WALKING , *SPEED measurements , *CENTRAL nervous system physiology - Abstract
Individuals with peripheral vestibulopathy are known to have difficulty with volitional head turns. This leads to differences in head and body turning kinematics, compared to those without vestibular dysfunction. Multiple sclerosis (MS), a neuro-inflammatory disease affecting the central nervous system, can cause vestibular dysfunction (dizziness, unsteadiness, gaze instability). However, head and trunk turning kinematics in people with MS (PwMS) have not been assessed. Will PwMS, demonstrate head and body kinematics alterations similar to individuals with a peripheral dysfunction compared to vestibular healthy individuals? Eleven individuals with a recent vestibular schwannoma resection (VSR), fourteen PwMS, and 10 healthy control (HC) participants were fitted with head and trunk worn inertial measurement units (IMUs) and performed walking and turning tasks. Head and trunk peak turning speed and amplitude were extracted. Regression models controlling for gait speed were fit per outcome with post hoc corrections applied to significant models. Yaw plane head turn speed and amplitude were significantly less in the VSR group compared to HC. Pitch plane head turn amplitude was significantly smaller in PwMS compared to HC (p = 0.04), however pitch plane speed did not differ between the groups. There was no difference between PwMS and the VSR group in yaw or pitch plane speed and amplitude. Both PwMS and the VSR group turned significantly slower than HC during the 180d body turn as measured at the head and trunk (head speed model p = 0.009 and <0.001; trunk speed model p < 0.001 for both groups) however the MS and VSR groups did not differ from each other. Turning kinematics while walking in PwMS are altered compared to HC and are similar to individuals with unilateral vestibular hypofunction. Centrally mediated vestibular dysfunction in PwMS may alter movement kinematics and should be considered during examination and treatment. • People with MS have turning kinematics similar to people with vestibular loss (78). • Turning kinematics differ in people with multiple sclerosis compared to controls (81). • Centrally mediated vestibular dysfunction may alter movement kinematics (71). [ABSTRACT FROM AUTHOR]
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- 2023
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21. COMPARISON OF TRUNK CONTROL, MANUAL DEXTERITY, AND REACTION TIME ACCORDING TO DIFFERENT STATUS OF BALANCE IN PEOPLE WITH PARKINSON DISEASE.
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YAKUT, Hatice, BEKAR, Zülal, MADEN, Tuba, and KUTLUHAN, Süleyman
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REACTION time , *PARKINSON'S disease , *CENTRAL nervous system physiology , *DISABILITIES , *PARKINSONIAN disorders - Abstract
Objective This study aims to compare trunk control, manual dexterity, and reaction time according to different balance states in people with Parkinson's Disease (PwPD). Material and Method A total of 25 PwPD, 6 of whom were women, were included in the study. Individuals were divided into the Moderate-risk group (n=11) and the Low-risk group (n=14) according to the Berg Balance Scale (BBS) cut-off scores. To evaluate trunk control and functions, static and dynamic sitting balance were evaluated with the Trunk Impairment Scale (TIS), which consists of trunk coordination sub-parameters. Hand grip strength was measured with the Jamar hand dynamometer, manual dexterity was measured bilaterally with the Purdue Pegboard Test, and hand reaction time was measured bilaterally with the the Ruler Drop Test. Results When the groups were compared for trunk control, there was a significant difference in the dynamic sitting subparameter and the total score of the trunk impairment scale in favor of the low-risk group (p=0.030, p=0.005). However, there was no difference between the groups in static sitting and coordination sub-parameters (p=0.181, p=0.558). There was no difference between the groups in the grip strength, dexterity, and reaction time of both hands (p>0.05). Conclusion While the dynamic sitting balance and trunk impairment of the moderate-risk balance group was worse than the low-risk group, manual dexterity and reaction time were similar. Further studies are needed to examine manual dexterity for trunk and distal mobility, which play a key role in proximal stabilization and balance in PwPD. [ABSTRACT FROM AUTHOR]
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- 2023
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22. Central sensitization in CRPS patients with widespread pain: a cross-sectional study.
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Schoenmacker, Iara De, Mollo, Anna, Scheuren, Paulina Simonne, Sirucek, Laura, Brunner, Florian, Schweinhardt, Petra, Curt, Armin, Rosner, Jan, and Hubli, Michèle
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CENTRAL nervous system physiology , *PAIN measurement , *NEURALGIA , *CROSS-sectional method , *QUANTITATIVE research , *PAIN threshold , *RESEARCH funding , *COMPLEX regional pain syndromes , *PHENOTYPES , *HYPERALGESIA , *PSYCHOLOGICAL distress - Abstract
Objective Widespread pain hypersensitivity and enhanced temporal summation of pain (TSP) are commonly reported in patients with complex regional pain syndrome (CRPS) and discussed as proxies for central sensitization. This study aimed to directly relate such signs of neuronal hyperexcitability to the pain phenotype of CRPS patients. Methods Twenty-one CRPS patients and 20 healthy controls (HC) were recruited. The pain phenotype including spatial pain extent (assessed in % body surface) and intensity were assessed and related to widespread pain hypersensitivity, TSP, and psychological factors. Quantitative sensory testing (QST) was performed in the affected, the contralateral and a remote (control) area. Results CRPS patients showed decreased pressure pain thresholds in all tested areas (affected: t(34) = 4.98, P < .001, contralateral: t(35) = 3.19, P = .005, control: t(31) = 2.65, P = .012). Additionally, patients showed increased TSP in the affected area (F(3,111) = 4.57, P = .009) compared to HC. TSP was even more enhanced in patients with a high compared to a low spatial pain extent (F(3,51) = 5.67, P = .008), suggesting pronounced spinal sensitization in patients with extended pain patterns. Furthermore, the spatial pain extent positively correlated with the Bath Body Perception Disturbance Scale (ρ = 0.491; P = .048). Conclusions Overall, we provide evidence that the pain phenotype in CRPS, that is, spatial pain extent, might be related to sensitization mechanism within the central nociceptive system. This study points towards central neuronal excitability as a potential therapeutic target in patients with more widespread CRPS. [ABSTRACT FROM AUTHOR]
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- 2023
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23. Acute effects of conventional versus wide‐pulse neuromuscular electrical stimulation on quadriceps evoked torque and neuromuscular function.
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Espeit, Loïc, Luneau, Eric, Brownstein, Callum G., Gondin, Julien, Millet, Guillaume Y., Rozand, Vianney, Maffiuletti, Nicola A., and Lapole, Thomas
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CENTRAL nervous system physiology , *QUADRICEPS muscle physiology , *EVOKED potentials (Electrophysiology) , *NEUROPHYSIOLOGY , *ELECTROPHYSIOLOGY , *COMPARATIVE studies , *ELECTRIC stimulation , *RESEARCH funding - Abstract
Purpose: The effectiveness of a neuromuscular electrical stimulation (NMES) program is proportional to the level of evoked torque, which can be achieved with either conventional or wide‐pulse stimulations. The aim of this study was to compare evoked torque, objective fatigability, and related peripheral and central alterations, as well as changes in central nervous system (CNS) excitability induced by an acute session of conventional versus wide‐pulse NMES. Methods: Seventeen young men underwent three 20‐min NMES sessions: conventional (0.2 ms/50 Hz), wide‐pulse at 50 Hz (1 ms/50 Hz), and wide‐pulse at 100 Hz (1 ms/100 Hz). Neuromuscular measurements (i.e., maximal voluntary contraction, voluntary activation, evoked responses to femoral nerve stimulation, and CNS excitability) were performed on the right quadriceps femoris muscle before and after each NMES session. CNS excitability was measured using transcranial magnetic, thoracic, and transcutaneous spinal cord stimulations. Results: The level of evoked torque was not significantly different between conventional and wide‐pulse protocols applied at the maximal tolerable current intensity. All NMES protocols induced objective fatigability (~14% decrease in maximal voluntary contraction torque, p < 0.001) associated with peripheral (decrease in doublet torque and potentiated M‐wave amplitude, p = 0.002 and p < 0.001, respectively) but not central (unchanged voluntary activation, p = 0.79) alterations. However, these acute changes did not differ between NMES protocols and none of the NMES protocols modified markers of CNS excitability. Conclusion: These results may allow to conjecture that chronic effects and treatment effectiveness could be comparable between conventional and wide‐pulse NMES. [ABSTRACT FROM AUTHOR]
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- 2023
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24. The conceptual basis of addiction memory, allostasis and dual processes, and the classical therapy of addiction.
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Chodkiewicz, Jan
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ALCOHOLISM , *ALLOSTASIS , *ALCOHOL drinking , *CENTRAL nervous system physiology , *SENSITIZATION (Neuropsychology) - Abstract
Purpose: In recent years, research has yielded new information regarding the impact of intense, long-term alcohol consumption on the development of permanent changes in the central nervous system. The present study examines the mechanisms related to the existence of addiction memory, sensitization and allostasis. A dual-process model was also created, which analyses the role of conscious and automatic mechanisms in the functioning of addicts. The aim of the article is to present these mechanisms and to consider the implications of their existence for the course of therapy. Views: The mechanisms analysed shed new light on some of the negative phenomena occurring during and after therapy, such as frequent abstinence after treatment, switching addictions, and returning to drinking after a long period of abstinence. The existence of these mechanisms should also change the character of addiction therapy, which has so far focused mainly on conscious aspects and ignored the existence of automatic ones. Attempts are already being made to implement the dual-process model in addiction therapy. Conclusions: A better understanding of the mechanisms resulting from the dual-process model can significantly influence perspectives regarding functioning in addiction and the course of therapy. These processes merit further research, as do possible therapeutic interventions based on them. [ABSTRACT FROM AUTHOR]
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- 2023
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25. Taking another look at the management of obesity.
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Brown, L.
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OBESITY treatment , *CENTRAL nervous system physiology , *PHARMACY , *PHARMACISTS , *BUPROPION - Abstract
Obesity is a common health condition that is increasing worldwide. Obesity is also a multifactorial condition that affects many physiological systems in the human body. Some include the following: central nervous system (CNS) effects, metabolic effects such as type 2 diabetes (T2D), various effects on the cardiovascular system (CVS), haematological effects and infertility in females. Treatment is suggested to be initiated by first making lifestyle changes such as increasing physical activity, decreasing caloric intake of foods, inclusion and accessibility to healthy foods (e.g. fruits, fibre, vegetables) and consuming foods of a lower glycaemic content. In addition to these interventions, pharmacological management strategies can also be considered adjuncts to managing obesity. These medicines (monotherapies/combined products) include amfepramone, cathine (syn D-norpseudoepherine), phendimetrazine, phentermine, orlistat, liraglutide, semaglutide, bupropion and the bupropion-naltrexone combination, and phentermine-topiramate combination. The pharmacist plays an essential role in identifying obese individuals, making suggestions for losing excess weight, suggesting lifestyle modifications, providing information about anti-obesity medicines and dispensing these medicines. [ABSTRACT FROM AUTHOR]
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- 2023
26. The Drivers of Diversity: Integrated genetic and hormonal cues regulate neural diversity.
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Hamid, Aisha, Gutierrez, Andrew, Munroe, Jordan, and Syed, Mubarak Hussain
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NEURAL stem cells , *CENTRAL nervous system , *GENETIC variation , *BIRTH order , *NERVOUS system , *GENE expression , *NEURAL circuitry , *CENTRAL nervous system physiology - Abstract
Proper functioning of the nervous system relies not only on the generation of a vast repertoire of distinct neural cell types but also on the precise neural circuitry within them. How the generation of highly diverse neural populations is regulated during development remains a topic of interest. Landmark studies in Drosophila have identified the genetic and temporal cues regulating neural diversity and thus have provided valuable insights into our understanding of temporal patterning of the central nervous system. The development of the Drosophila central complex, which is mostly derived from type II neural stem cell (NSC) lineages, showcases how a small pool of NSCs can give rise to vast and distinct progeny. Similar to the human outer subventricular zone (OSVZ) neural progenitors, type II NSCs generate intermediate neural progenitors (INPs) to expand and diversify lineages that populate higher brain centers. Each type II NSC has a distinct spatial identity and timely regulated expression of many transcription factors and mRNA binding proteins. Additionally, INPs derived from them show differential expression of genes depending on their birth order. Together type II NSCs and INPs display a combinatorial temporal patterning that expands neural diversity of the central brain lineages. We cover advances in current understanding of type II NSC temporal patterning and discuss similarities and differences in temporal patterning mechanisms of various NSCs with a focus on how cell-intrinsic and extrinsic hormonal cues regulate temporal transitions in NSCs during larval development. Cell extrinsic ligands activate conserved signaling pathways and extrinsic hormonal cues act as a temporal switch that regulate temporal progression of the NSCs. We conclude by elaborating on how a progenitor's temporal code regulates the fate specification and identity of distinct neural types. At the end, we also discuss open questions in linking developmental cues to neural identity, circuits, and underlying behaviors in the adult fly. [ABSTRACT FROM AUTHOR]
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- 2023
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27. High-resolution structural and functional retinal imaging in the awake behaving mouse.
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Feng, Guanping, Joseph, Aby, Dholakia, Kosha, Shang, Fei, Pfeifer, Charles W., Power, Derek, Padmanabhan, Krishnan, and Schallek, Jesse
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RETINAL imaging , *CENTRAL nervous system physiology , *LABORATORY mice , *ADAPTIVE optics , *MICE , *RETINA - Abstract
The laboratory mouse has provided tremendous insight to the underpinnings of mammalian central nervous system physiology. In recent years, it has become possible to image single neurons, glia and vascular cells in vivo by using head-fixed preparations combined with cranial windows to study local networks of activity in the living brain. Such approaches have also succeeded without the use of general anesthesia providing insights to the natural behaviors of the central nervous system. However, the same has not yet been developed for the eye, which is constantly in motion. Here we characterize a novel head-fixed preparation that enables high-resolution adaptive optics retinal imaging at the single-cell level in awake-behaving mice. We reveal three new functional attributes of the normal eye that are overlooked by anesthesia: 1) High-frequency, low-amplitude eye motion of the mouse that is only present in the awake state 2) Single-cell blood flow in the mouse retina is reduced under anesthesia and 3) Mouse retinae thicken in response to ketamine/xylazine anesthesia. Here we show key benefits of the awake-behaving preparation that enables study of retinal physiology without anesthesia to study the normal retinal physiology in the mouse. A high-resolution imaging apparatus that allows functional retinal imaging in awake and free moving mice was developed, allowing the study of the effect of anaesthesia on eye motion, blood flow and retinal thickness. [ABSTRACT FROM AUTHOR]
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- 2023
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28. Central androgen action reverses hypothalamic astrogliosis and atherogenic risk factors induced by orchiectomy and high-fat diet feeding in male mice.
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Dorfman, Mauricio D., Monfeuga, Thomas, Melhorn, Susan J., Kanter, Jenny E., Frey, Jeremy M., Fasnacht, Rachael D., Chandran, Anandhakumar, Lala, Emaad, Velasco, Inmaculada, Rubinow, Katya B., Meek, Thomas H., Schur, Ellen A., Bornfeldt, Karin E., and Thaler, Joshua P.
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HIGH-fat diet , *ANDROGEN receptors , *WESTERN diet , *CASTRATION , *GLIOSIS , *ANDROGENS , *CENTRAL nervous system physiology - Abstract
Hypogonadism in males confers elevated cardiovascular disease (CVD) risk by unknown mechanisms. Recent radiological evidence suggests that low testosterone (T) is associated with mediobasal hypothalamic (MBH) gliosis, a central nervous system (CNS) cellular response linked to metabolic dysfunction. To address mechanisms linking CNS androgen action to CVD risk, we generated a hypogonadal, hyperlipidemic mouse model with orchiectomy (ORX) combined with hepatic PCSK9 overexpression. After 4 wk of high-fat, high-sucrose diet (HFHS) consumption, despite equal body weights and glucose tolerance, androgen-deficient ORX mice had a more atherogenic lipid profile and increased liver and leukocyte inflammatory signaling compared with sham-operated control mice. Along with these early CVD risk indicators, ORX markedly amplified HFHS-induced astrogliosis in the MBH. Transcriptomic analysis further revealed that ORX and high-fat diet feeding induced upregulation of inflammatory pathways and downregulation of metabolic pathways in hypothalamic astrocytes. To interrogate the role of sex steroid signaling in the CNS in cardiometabolic risk and MBH inflammation, central infusion of T and dihydrotestosterone (DHT) was performed on ORX mice. Central DHT prevented MBH astrogliosis and reduced the liver inflammatory signaling and monocytosis induced by HFHS and ORX; T had a partial protective effect. Finally, a cross-sectional study in 41 adult men demonstrated a positive correlation between radiological evidence of MBH gliosis and plasma lipids. These findings demonstrate that T deficiency in combination with a Western-style diet promotes hypothalamic gliosis concomitant with increased atherogenic risk factors and provide supportive evidence for regulation of lipid metabolism and cardiometabolic risk determinants by the CNS action of sex steroids. NEW & NOTEWORTHY This study provides evidence that hypothalamic gliosis is a key early event through which androgen deficiency in combination with a Western-style diet might lead to cardiometabolic dysregulation in males. Furthermore, this work provides the first evidence in humans of a positive association between hypothalamic gliosis and LDL-cholesterol, advancing our knowledge of CNS influences on CVD risk progression. [ABSTRACT FROM AUTHOR]
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- 2023
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29. Regulatory T lymphocytes as a therapy for ischemic stroke.
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Wang, Miao, Thomson, Angus W., Yu, Fang, Hazra, Rimi, Junagade, Aditi, and Hu, Xiaoming
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REGULATORY T cells , *ISCHEMIC stroke , *HOMEOSTASIS , *IMMUNOSUPPRESSION , *CELL communication , *STROKE , *CENTRAL nervous system physiology - Abstract
Unrestrained excessive inflammatory responses exacerbate ischemic brain injury and impede post-stroke brain recovery. CD4+CD25+Foxp3+ regulatory T (Treg) cells play important immunosuppressive roles to curtail inflammatory responses and regain immune homeostasis after stroke. Accumulating evidence confirms that Treg cells are neuroprotective at the acute stage after stroke and promote brain repair at the chronic phases. The beneficial effects of Treg cells are mediated by diverse mechanisms involving cell–cell interactions and soluble factor release. Multiple types of cells, including both immune cells and non-immune CNS cells, have been identified to be cellular targets of Treg cells. In this review, we summarize recent findings regarding the function of Treg cells in ischemic stroke and the underlying cellular and molecular mechanisms. The protective and reparative properties of Treg cells endorse them as good candidates for immune therapy. Strategies that boost the numbers and functions of Treg cells have been actively developing in the fields of transplantation and autoimmune diseases. We discuss the approaches for Treg cell expansion that have been tested in stroke models. The application of these approaches to stroke patients may bring new hope for stroke treatments. [ABSTRACT FROM AUTHOR]
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- 2023
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30. Normal glymphatic system function in patients with new daily persistent headache using diffusion tensor image analysis along the perivascular space.
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Zhang, Xue, Wang, Wei, Zhang, Xueyan, Bai, Xiaoyan, Yuan, Ziyu, Zhang, Peng, Bai, Ruiliang, Jiao, Bingjie, Zhang, Yingkui, Li, Zhiye, Tang, Hefei, Zhang, Yaqing, Yu, Xueying, Wang, Yonggang, and Sui, Binbin
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CENTRAL nervous system physiology , *LYMPHATIC physiology , *BRAIN , *NEUROPSYCHOLOGY , *CONFIDENCE intervals , *CROSS-sectional method , *MAGNETIC resonance imaging , *DESCRIPTIVE statistics , *RESEARCH funding , *HEADACHE - Abstract
Objectives: To investigate the glymphatic function in patients with new daily persistent headache (NDPH) using the diffusion tensor image analysis along the perivascular space (DTI‐ALPS) method. Background: NDPH, a rare and treatment‐refractory primary headache disorder, is poorly understood. There is limited evidence to suggest that headaches are associated with glymphatic dysfunction. Thus far, no studies have evaluated glymphatic function in patients with NDPH. Methods: In this cross‐sectional study conducted in the Headache Center of Beijing Tiantan Hospital, patients with NDPH and healthy controls were enrolled. All participants underwent brain magnetic resonance imaging examinations. Clinical characteristics and neuropsychological evaluation were examined in patients with NDPH. ALPS indexes for both hemispheres were measured to determine the glymphatic system function in patients with NDPH and healthy controls. Results: In total, 27 patients with NDPH (14 males, 13 females; age [mean ± standard deviation (SD)]: 36.6 ± 20.6) and 33 healthy controls (15 males, 18 females; age [mean ± SD]: 36.0 ± 10.8) were included in the analysis. No significant differences between groups were observed in the left ALPS index (1.583 ± 0.182 vs. 1.586 ± 0.175, mean difference = 0.003, 95% confidence interval [CI] of difference = −0.089 to 0.096, p = 0.942), or right ALPS index (1.578 ± 0.230 vs. 1.559 ± 0.206, mean difference = −0.027, 95% CI of difference = −0.132 to 0.094, p = 0.738). Additionally, ALPS indexes were not correlated with clinical characteristics or neuropsychiatric scores. Conclusion: No glymphatic dysfunction was detected in patients with NDPH by means of the ALPS method. Additional studies with larger samples are needed to confirm these preliminary findings and improve the understanding of glymphatic function in NDPH. [ABSTRACT FROM AUTHOR]
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- 2023
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31. اثر ۶ هفته تمرین تناوبی شدید و تعلیق پاهای عقبی روی تغییرات در GFAP و 4 سلولهای بنیادی گلیالی مغز موشهای صحرایی نر سالم.
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ذبیح الله قدم پور, واز گن میناسیان, and علی کاظمی
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CENTRAL nervous system physiology , *NEURAL physiology , *PROTEIN metabolism , *EXERCISE physiology , *DATA analysis , *HIGH-intensity interval training , *NEUROGLIA , *DESCRIPTIVE statistics , *RATS , *MONOCLONAL antibodies , *ANIMAL experimentation , *STATISTICS , *STEM cells , *HIPPOCAMPUS (Brain) - Abstract
Background & Aims: Nerve stem cell transplantation is one of the effective strategies for repairing nerve lesions. Oligodendrocytes are myelinated cells located in the central nervous system and are involved in the formation of myelin axons (8). Oligodendrocytes express O-A proteins, especially O4, which is a marker for the cell body and oligodendrocyte processes, during differentiation and maturation in the central nervous system (29). The results of some studies have shown that glial cells that express only O4 protein have the potential to become precursors of astrocytes and oligodendrocytes and can increase the growth stages in stem cells (29). Glial fibrillary acid protein (GFAP) is known as a specific marker for the identification of astrocytes in the central nervous system. This protein is the main cytoskeleton constituent of astrocytes (27) and plays an important role in maintaining, repairing and maintaining the white matter integrity of the central nervous system as well as the blood-brain barrier (35). The aim of this study was to compare the effect of High intensity interval training with hind limb suspension on the level of GFAP and O4 in glial and neuronal stem cell of male rats. Methods: Twenty-four male wistar rats (body weight = 189.25 ± 5.71g.) were randomly divided into four groups: HIIT+HLS (n= 6), HIIT (n= 6), HLS (n= 6) or CON (n= 6). The exercise protocol was performed on a rodent treadmill for 6 weeks, 5 sessions per week. The rats were sampled and studied 24 h after last training session. Glial fibrillary acidic protein (GFAP) and monoclonal antibody O4 (O4) were analyzed before and after the training interventions. To suspend the lower limb, the animal's tail was first cleaned and dried using cotton and alcohol. Then two-thirds of the mouse tail was taped longitudinally from the beginning to the end third. Next, three pieces of kinesio-tape were placed transversely on the mouse tail, so that normal blood flow was not disturbed. We attached the upper end of the kinesio-tape to the suspension hook and then has been attached the hook to the cage movable bar chain so that the angle between the animal's chest and the floor of the cage is 30 degrees and the mouse legs do not come into contact with the floor of the cage. The suspension system, including a movable bar, pulley and hook, was mounted on top and on both parallel sides of the cage, allowing the animal to have full access to all parts of the cage by moving freely around a 360-degree axis. Data analysis was used using Shapiro-Wilk and Levine tests to investigate the natural distribution of data and homogeneity of variances and one-way and post-hoc Bonferroni statistics to test research hypotheses. Results: The results suggested that the percentage of changes in the amounts of fibrillary acidic protein of the cerebral hippocampus of the brain in the intense interval training group + group under the conditions of the hind legs compared to the control group showed a significant decrease (p≥0.001). Also, the percentage of changes in cerebral hippocampal glial fibrillary acid protein in the lower extremity suspension group increased significantly more than the control group (p≥0.001), but the percentage of changes in this protein in the intense interval training group compared to the group There was no significant difference in control (p≥1,000). The results of the data obtained from the percentage of changes in the O4 protein of the cerebral hippocampus of the groups showed that this change was significantly lower in the group of intense interval training with the conditions of the hind limb suspended than the control group (p≥0.001). Also, the percentage of O4 changes in the cerebral hippocampus in the lower extremity suspension group was significantly higher than the control (p≥0.001). In addition, the percentage of changes in the intense interval training group was not significantly different from the control group (p≥0.465). Conclusion: The results of this study revealed that HIIT+HLS was being able to prevent damage to the cells of the central nervous system and direct the neural stem cells towards the production of neurons, astrocyte and oligodendrocyte. Mesenchymal stem cells are currently the main choice for cellular treatment of neuropsychiatric diseases. Mechanical stimuli have been reported to play a decisive role in the final fate of stem cells and their cell differentiation pathways, so that the path and flow of induced signals and activated factors determine cellular fate in time, position, and mediate an appropriate number (36). Studies have shown that the proliferation, differentiation, and cytoskeleton organization of stem cells are affected by microgravity and tend to produce neurons or nerve cells (31). Astroglia cells also act as neuronal stem cells and participate in neurogenesis. Evidence suggests a very important role for these cells during plasticity. These cells are involved in the neurogenesis of the adult mammalian brain in the ventricular region, and in the sub-granular region and the olfactory bulb. On the other hand, previous research has shown that lactate production during intense interval trainings and suspension of hind legs can play an important role in the development of oligodendrocytes and myelination, so that increasing lactate production as a substrate in myelination, and used by the nervous system. Considering this issue, it is possible to use this exercise mode in the condition of lower limb suspension as a treatment method or non-pharmacological supplement effective in neuromuscular disorders and other related diseases, to enhance fitness in athletes, improve injury and also prevention of adverse effects of being in weightlessness, especially on space missions. In general, the results show that intense interval training with hind leg suspension conditions had a greater effect on health and no damage to the hippocampus of the brain of a healthy male rat than other groups (intense interval, suspension or control group). Since no research has been done on the effect of intense interval training under the conditions of hind limb suspension on cellular changes in the hippocampus and human brain, judgment in this regard needs further study. Findings of this study may help in the rehabilitation process of people with neuromotor disorders, injured athletes, the elderly, sedentary people, as well as the conditioning program of athletes in various sports to adapt to the use of such exercises. [ABSTRACT FROM AUTHOR]
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- 2023
32. Secreted Amyloid Precursor Protein Alpha (sAPPα Regulates the Cellular Proteome and Secretome of Mouse Primary Astrocytes.
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Peppercorn, Katie, Kleffmann, Torsten, Hughes, Stephanie M., and Tate, Warren P.
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AMYLOID beta-protein precursor , *CENTRAL nervous system physiology , *DEVELOPMENTAL neurobiology , *ASTROCYTES , *ALZHEIMER'S disease , *MYELIN sheath - Abstract
Secreted amyloid precursor protein alpha (sAPPα), processed from a parent mammalian brain protein, amyloid precursor protein, can modulate learning and memory. Recently it has been shown to modulate the transcriptome and proteome of human neurons, including proteins with neurological functions. Here, we analysed whether the acute administration of sAPPα facilitated changes in the proteome and secretome of mouse primary astrocytes in culture. Astrocytes contribute to the neuronal processes of neurogenesis, synaptogenesis and synaptic plasticity. Cortical mouse astrocytes in culture were exposed to 1 nM sAPPα, and changes in both the whole-cell proteome (2 h) and the secretome (6 h) were identified with Sequential Window Acquisition of All Theoretical Fragment Ion Spectra–Mass Spectrometry (SWATH-MS). Differentially regulated proteins were identified in both the cellular proteome and secretome that are involved with neurologically related functions of the normal physiology of the brain and central nervous system. Groups of proteins have a relationship to APP and have roles in the modulation of cell morphology, vesicle dynamics and the myelin sheath. Some are related to pathways containing proteins whose genes have been previously implicated in Alzheimer's disease (AD). The secretome is also enriched in proteins related to Insulin Growth Factor 2 (IGF2) signaling and the extracellular matrix (ECM). There is the promise that a more specific investigation of these proteins will help to understand the mechanisms of how sAPPα signaling affects memory formation. [ABSTRACT FROM AUTHOR]
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- 2023
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33. c.754T>A homozygous mutation described for the first time in three Moroccan patients with Gaucher disease.
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Zouiri, Ghizlane, Rhouda, Hajar, and Kriouile, Yamna
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GAUCHER'S disease , *CENTRAL nervous system physiology , *PHENOTYPES , *GENOTYPES , *STATISTICAL correlation - Abstract
Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase (GBA) deficiency. There are three subcategories of GD: Type 1 is characterized by the absence of primary central nervous system involvement; type 2 is an acute neuropathic disorder; and type 3 is chronic neuropathic. The correlation between genotype and phenotype is sometimes difficult to establish. The F213I (c.754T> A p.Phe252Ile) mutation was reported to be a unique mutation in Asia. To our knowledge, this is the first time the c.754T> A p.(Phe252Ile) mutation (homozygous state) is reported in a Moroccan population and is associated with GD type 2 (two patients) and GD type 3 (one patient). [ABSTRACT FROM AUTHOR]
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- 2024
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34. Central sensitization in patients with deep endometriosis.
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Quintas-Marquès, Lara, Martínez-Zamora, Maria-Ángeles, Camacho, Marta, Gràcia, Meritxell, Rius, Mariona, Ros, Cristina, Carrión, Ana, and Carmona, Francisco
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CENTRAL nervous system physiology , *COMPETENCY assessment (Law) , *ENDOMETRIOSIS , *CHRONIC pain , *PERIMENOPAUSE , *STATISTICAL power analysis , *KRUSKAL-Wallis Test , *PELVIC pain , *CROSS-sectional method , *TERTIARY care , *HEALTH surveys , *RISK assessment , *COMPARATIVE studies , *PSYCHOLOGICAL tests , *T-test (Statistics) , *QUALITY of life , *QUESTIONNAIRES , *CHI-squared test , *DESCRIPTIVE statistics , *DATA analysis software , *DISEASE risk factors , *DISEASE complications - Published
- 2023
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35. Axonal Guidance Using Biofunctionalized Straining Flow Spinning Regenerated Silk Fibroin Fibers as Scaffold.
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Castro-Domínguez, Cristina, Lozano-Picazo, Paloma, Álvarez-López, Aroa, Garrote-Junco, Javier, Panetsos, Fivos, Guinea, Gustavo V., Elices, Manuel, Rojo, Francisco Javier, González-Nieto, Daniel, Colchero, Luis, Ramos, Milagros, and Pérez-Rigueiro, José
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SILK fibroin , *SPINAL cord injuries , *BIOMATERIALS , *NEURONS , *CENTRAL nervous system physiology - Abstract
After an injury, the limited regenerative capacity of the central nervous system makes the reconnection and functional recovery of the affected nervous tissue almost impossible. To address this problem, biomaterials appear as a promising option for the design of scaffolds that promote and guide this regenerative process. Based on previous seminal works on the ability of regenerated silk fibroin fibers spun through the straining flow spinning (SFS) technique, this study is intended to show that the usage of functionalized SFS fibers allows an enhancement of the guidance ability of the material when compared with the control (nonfunctionalized) fibers. It is shown that the axons of the neurons not only tend to follow the path marked by the fibers, in contrast to the isotropic growth observed on conventional culture plates, but also that this guidance can be further modulated through the biofunctionalization of the material with adhesion peptides. Establishing the guidance ability of these fibers opens the possibility of their use as implants for spinal cord injuries, so that they may represent the core of a therapy that would allow the reconnection of the injured ends of the spinal cord. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
36. INTRA-STRIATUM LO DOXAM I DE PRODUCED CONDITIONING PLACE PREFERENCE IN RATS VIA GPR35 INDEPENDENT MECHANISMS.
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Díaz-Barba, Alejandro, Guerrero-Alba, Raquel, Quintanar, J. Luis, and Marichal-Cancino, Bruno A.
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CENTRAL nervous system physiology , *ANIMAL experimentation , *CELL receptors , *STEREOTAXIC techniques , *DESCRIPTIVE statistics , *RESEARCH funding , *MICE - Abstract
The function of the protein-coupled receptor 35 (GPR35) in the central nervous system (CNS) remains largely unknown. Due to its expression in the ventral striatum, a key area in the brain reward system, the function of GPR35 in reinforcing actions is questioning. To analyze if activation of GPR35 in the ventral striatum is related to reinforcing actions, male Wistar rats (250-300 g) received stereotaxic surgery to place guide cannulae in the ventral striatum. Lodoxamide (a full rat-GPR35 agonist) or vehicle (DMSO 10%) were injected (intra-ventral-striatum) in the absence and during the pretreatment with ML-194 (a selective GPR35 antagonist). Lodoxamide (100 pmol) induced a significant increment in preference for the drug-conditioning chamber (p < 0.05), but not vehicle or ML-194 per se (p > 0.05). On the other hand, the pretreatment with ML-194 did not prevent lodoxamide's reinforcing effects. Thus, the reinforcing actions of lodoxamide (intra-ventral-striatum) involve mechanisms likely independent of GPR35 which remains to be identified; and a role for GPR35 in the brain reward systems (at least in ventral striatum) seems improbable. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
37. The Emerging Role of Vitamin D in Neurological Health and Disease.
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Noor, Amna and Ali Shah, Syed Imran
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CEREBROVASCULAR disease risk factors , *ALZHEIMER'S disease risk factors , *CENTRAL nervous system physiology , *PERIPHERAL nervous system physiology , *AUTONOMIC nervous system physiology , *VITAMIN D metabolism , *COGNITION disorder risk factors , *MULTIPLE sclerosis risk factors , *VITAMIN D deficiency , *RISK assessment , *NEUROPHYSIOLOGY , *NEURAL development , *BIOCHEMISTRY , *PARKINSON'S disease , *NEUROLOGICAL disorders , *GENE expression , *CHOLECALCIFEROL , *AMYOTROPHIC lateral sclerosis , *MOLECULAR structure , *DOPAMINE , *VITAMIN D , *BIOMARKERS , *NERVE growth factor , *ACETYLCHOLINE , *GABA , *DIET , *COGNITION , *DISEASE risk factors , *DISEASE complications - Abstract
Vitamin D has come up as a pluripotent biochemical modulator of several systemic functions including its wellestablished musculoskeletal effects functioning as well as other key roles in nervous, cardiac, immune, vascular, and endocrinological systems. It undergoes metabolic activation in the skin, liver, and kidneys to exert its systemic actions primarily through Vitamin D receptor-mediated gene expression. In recent times, the involvement of Vitamin D has been documented in the regulation of neurotrophins, neural differentiation, and maturation, and the synthesis of neuromodulators including acetylcholine, dopamine, and gamma-aminobutyric acid. Clinical studies have also highlighted the involvement of Vitamin D in neurological disorders, thereby underscoring its potential in the clinical management of such disorders. Further, research is required to determine the multipronged roles of Vitamin D and its molecular pathways in neurophysiology for the potential prevention and treatment of neurological dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
38. The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders.
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Anand, Nikhilesh, Gorantla, Vasavi Rakesh, and Chidambaram, Saravana Babu
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CENTRAL nervous system physiology , *NEUROBEHAVIORAL disorders , *BLOOD-brain barrier , *PATHOLOGICAL physiology , *DYSBIOSIS , *FECAL microbiota transplantation - Abstract
Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut–brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, and autonomic nervous systems. Recent studies have bolstered the involvement of dysfunctional MGB axis signaling in the pathophysiology of several neurodegenerative, neurodevelopmental, and neuropsychiatric disorders (NPDs). Several investigations on the dynamic microbial system and genetic–environmental interactions with the gut microbiota (GM) have shown that changes in the composition, diversity and/or functions of gut microbes (termed "gut dysbiosis" (GD)) affect neuropsychiatric health by inducing alterations in the signaling pathways of the MGB axis. Interestingly, both preclinical and clinical evidence shows a positive correlation between GD and the pathogenesis and progression of NPDs. Long-term GD leads to overstimulation of hypothalamic–pituitary–adrenal (HPA) axis and the neuroimmune system, along with altered neurotransmitter levels, resulting in dysfunctional signal transduction, inflammation, increased oxidative stress (OS), mitochondrial dysfunction, and neuronal death. Further studies on the MGB axis have highlighted the significance of GM in the development of brain regions specific to stress-related behaviors, including depression and anxiety, and the immune system in the early life. GD-mediated deregulation of the MGB axis imbalances host homeostasis significantly by disrupting the integrity of the intestinal and blood–brain barrier (BBB), mucus secretion, and gut immune and brain immune functions. This review collates evidence on the potential interaction between GD and NPDs from preclinical and clinical data. Additionally, we summarize the use of non-therapeutic modulators such as pro-, pre-, syn- and post-biotics, and specific diets or fecal microbiota transplantation (FMT), which are promising targets for the management of NPDs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
39. Sensitivity to movement‐evoked pain, central sensitivity symptoms, and pro‐nociceptive profiles in people with chronic shoulder pain: A parallel‐group cross‐sectional investigation.
- Author
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Othman, Rani, Swain, Nicola, Tumilty, Steve, Jayakaran, Prasath, and Mani, Ramakrishnan
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SHOULDER physiology , *CENTRAL nervous system physiology , *SHOULDER pain , *CHRONIC pain , *EVALUATION of medical care , *CROSS-sectional method , *LIFTING & carrying (Human mechanics) , *PAIN threshold , *SENSORY stimulation , *COMPARATIVE studies , *PATIENTS' attitudes , *BODY movement , *QUESTIONNAIRES , *SENSITIVITY & specificity (Statistics) , *NOCICEPTIVE pain , *PAIN management - Abstract
Objective: To investigate whether sensitivity to movement‐evoked pain (SMEP), central sensitivity symptom burden, and quantitative sensory testing (QST) outcomes differ between healthy controls and people with chronic shoulder pain. Methods: People with chronic shoulder pain (n = 39) and healthy controls (n = 26) completed validated questionnaires measuring demographic, pain characteristics, psychological factors, social support, sleep quality, central sensitivity inventory (CSI), and physical activity levels. A blinded assessor administered QST measuring pressure pain threshold, temporal summation, conditioned pain modulation, and cold hyperalgesia. All participants performed repeated lifting of weighted canisters and reported severity of pain over successive lifts of the weighted canisters. Between‐group differences in the QST, SMEP and CSI scores were investigated. Demographic and psychosocial variables were adjusted in the analyses. Results: Dynamic mechanical allodynia, mechanical temporal summation, movement‐evoked pain scores, SMEP index, and CSI scores were significantly (p ≤ 0.05) higher in the chronic shoulder pain group than in healthy controls. A significant proportion of people with chronic shoulder pain presented with pro‐nociceptive profiles and experienced higher pain severity, interference, and disability. Conclusions: People with chronic shoulder pain displayed symptoms and signs of central sensitization. Future research should investigate the predictive role of central sensitization on clinical outcomes in shoulder pain. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
40. Automated detection of GFAP-labeled astrocytes in micrographs using YOLOv5.
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Huang, Yewen, Kruyer, Anna, Syed, Sarah, Kayasandik, Cihan Bilge, Papadakis, Manos, and Labate, Demetrio
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DEEP learning , *ASTROCYTES , *CENTRAL nervous system physiology , *IMAGE analysis - Abstract
Astrocytes, a subtype of glial cells with a complex morphological structure, are active players in many aspects of the physiology of the central nervous system (CNS). However, due to their highly involved interaction with other cells in the CNS, made possible by their morphological complexity, the precise mechanisms regulating astrocyte function within the CNS are still poorly understood. This knowledge gap is also due to the current limitations of existing quantitative image analysis tools that are unable to detect and analyze images of astrocyte with sufficient accuracy and efficiency. To address this need, we introduce a new deep learning framework for the automated detection of GFAP-immunolabeled astrocytes in brightfield or fluorescent micrographs. A major novelty of our approach is the applications of YOLOv5, a sophisticated deep learning platform designed for object detection, that we customized to derive optimized classification models for the task of astrocyte detection. Extensive numerical experiments using multiple image datasets show that our method performs very competitively against both conventional and state-of-the-art methods, including the case of images where astrocytes are very dense. In the spirit of reproducible research, our numerical code and annotated data are released open source and freely available to the scientific community. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
41. T-cell surveillance of the human brain in health and multiple sclerosis.
- Author
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Smolders, Joost, van Luijn, Marvin M., Hsiao, Cheng-Chih, and Hamann, Jörg
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MULTIPLE sclerosis , *MYELIN proteins , *MENINGES , *CEREBROSPINAL fluid , *CENTRAL nervous system , *AUTOIMMUNE diseases , *T cells , *CENTRAL nervous system physiology - Abstract
Circulating and tissue-resident T cells collaborate in the protection of tissues against harmful infections and malignant transformation but also can instigate autoimmune reactions. Similar roles for T cells in the brain have been less evident due to the compartmentized organization of the central nervous system (CNS). In recent years, beneficial as well as occasional, detrimental effects of T-cell-targeting drugs in people with early multiple sclerosis (MS) have increased interest in T cells patrolling the CNS. Next to studies focusing on T cells in the cerebrospinal fluid, phenotypic characteristics of T cells located in the perivascular space and the meninges as well as in the parenchyma in MS lesions have been reported. We here summarize the current knowledge about T cells infiltrating the healthy and MS brain and argue that understanding the dynamics of physiological CNS surveillance by T cells is likely to improve the understanding of pathological conditions, such as MS. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
42. Central sensitization and functioning in patients with chronic low back pain: A cross-sectional and longitudinal study.
- Author
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Echeita, Jone Ansuategui, Schiphorst Preuper, Henrica R., Dekker, Rienk, and Reneman, Michiel F.
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CENTRAL nervous system physiology , *CHRONIC pain , *LUMBAR pain , *SCIENTIFIC observation , *EMPLOYMENT of people with disabilities , *FUNCTIONAL status , *CROSS-sectional method , *MULTIPLE regression analysis , *LIFTING & carrying (Human mechanics) , *WORK capacity evaluation , *HEALTH care teams , *HEART beat , *DESCRIPTIVE statistics , *LONGITUDINAL method , *HYPERALGESIA , *DISEASE complications - Abstract
BACKGROUND: Central sensitization (CS) is present in a subgroup of patients with chronic low back pain (CLBP). Studies on the relationship between CS and functioning have limited operationalizations of CS and functioning. OBJECTIVE: To determine whether CS was related to functioning in patients with CLBP (cross-sectional); and to determine whether changes in CS were related to changes in functioning (longitudinal). METHODS: An observational prospective cohort study with data collected at baseline and discharge of an interdisciplinary pain rehabilitation program was executed. CS indicators: CS Inventory part A (CSI-A), quantitative sensory testing (QST), root mean square of successive differences of heart-rate variability (RMSSD). Functioning measures: lifting capacity, physical functioning subscale of Rand36 (Rand36-PF), Work Ability Score (WAS), Pain Disability Index (PDI). Main analyses included correlation and multiple regression controlling for confounders; cross-sectional with baseline data and longitudinal with deltas (Δ). RESULTS: 76 patients with primary CLBP participated at baseline and 56 at discharge. Most associations were weak (cross-sectional rpartial=-0.30-0.24; longitudinal rpartial=-0.37-0.44). Cross-sectional multiple regression significant associations: mechanical pain threshold-QST and lifting capacity (rpartial=-0.39), parasympathetic/vagal tone-RMSSD and physical functioning-Rand36-PF (rpartial= 0.26). Longitudinal multiple regression significant associations: Δ parasympathetic/vagal tone-RMSSD and Δ lifting capacity (rpartial = 0.48), ΔCSI-A and Δdisability-PDI (rpartial= 0.36). Cross-sectional and longitudinal final regression models explained 24.0%-58.3% and 13.3%-38.0% of total variance. CONCLUSION: CS was weakly related to functioning, and decreases in CS were weakly-moderately related to increases in functioning. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
43. Lipoxygenase Metabolism: Critical Pathways in Microglia-mediated Neuroinflammation and Neurodevelopmental Disorders.
- Author
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Chen, Shuli and Zou, Haidong
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- *
MICROGLIA , *NEUROINFLAMMATION , *CENTRAL nervous system physiology , *NEURAL development , *FATTY acid oxidation , *UNSATURATED fatty acids , *CENTRAL nervous system - Abstract
As innate immune cells of the central nervous system (CNS), microglia are involved in the physiological processes of the CNS, including neural development and maintenance of homeostasis, and in the occurrence and development of most CNS diseases. Lipoxygenases (LOXs) are a family of non-heme, iron-containing enzymes that generate lipid mediators that regulate cellular inflammation by catalyzing the oxidation of polyunsaturated fatty acids. Many previous studies have demonstrated the indispensable role of the LOX pathway in microglia-mediated neuroinflammation, especially the 5-LOX and 12/15-LOX pathways. Emerging evidence indicates that the LOX pathway is also implicated in physiological processes, such as synaptic pruning and synaptic phagocytosis mediated by microglia, and that deficiency can contribute to neurodevelopmental disorders. The present review summarizes the impact of the LOX pathway on microglia-related physiological and pathological processes in the CNS and describes the potential for inhibition of the LOX pathway as a future strategy for the treatment of CNS diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
44. Generation of Human iPSC-Derived Astrocytes with a mature star-shaped phenotype for CNS modeling.
- Author
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Voulgaris, Dimitrios, Nikolakopoulou, Polyxeni, and Herland, Anna
- Subjects
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ASTROCYTES , *PLURIPOTENT stem cells , *CD54 antigen , *INDUCED pluripotent stem cells , *GLUTAMATE transporters , *CENTRAL nervous system physiology , *HUMAN stem cells , *STEM cells - Abstract
The generation of astrocytes from human induced pluripotent stem cells has been hampered by either prolonged differentiation—spanning over two months—or by shorter protocols that generate immature astrocytes, devoid of salient mature astrocytic traits pivotal for central nervous system (CNS) modeling. We directed stable hiPSC-derived neuroepithelial stem cells to human iPSC-derived Astrocytes (hiAstrocytes) with a high percentage of star-shaped cells by orchestrating an astrocytic-tuned culturing environment in 28 days. We employed RT-qPCR and ICC to validate the astrocytic commitment of the neuroepithelial stem cells. To evaluate the inflammatory phenotype, we challenged the hiAstrocytes with the pro-inflammatory cytokine IL-1β (interleukin 1 beta) and quantitatively assessed the secretion profile of astrocyte-associated cytokines and the expression of intercellular adhesion molecule 1 (ICAM-1). Finally, we quantitatively assessed the capacity of hiAstrocytes to synthesize and export the antioxidant glutathione. In under 28 days, the generated cells express canonical and mature astrocytic markers, denoted by the expression of GFAP, AQP4 and ALDH1L1. In addition, the notion of a mature phenotype is reinforced by the expression of both astrocytic glutamate transporters EAAT1 and EAAT2. Thus, hiAstrocytes have a mature phenotype that encompasses traits critical in CNS modeling, including glutathione synthesis and secretion, upregulation of ICAM-1 and a cytokine secretion profile on a par with human fetal astrocytes. This protocol generates a multifaceted astrocytic model suitable for in vitro CNS disease modeling and personalized medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
45. In vivo peptide-based delivery of a gene-modifying enzyme into cells of the central nervous system.
- Author
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Allen, Jason K., Sutherland, Theresa C., Prater, Austin R., Geoffroy, Cédric G., and Pellois, Jean-Philippe
- Subjects
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CENTRAL nervous system , *GLIAL fibrillary acidic protein , *CENTRAL nervous system physiology , *CATIONIC lipids , *CELL receptors , *CELL culture , *GREEN fluorescent protein , *TRANSCRIPTION factors - Abstract
The article reports the In vivo peptide-based delivery of a gene-modifying enzyme into cells of the central nervous system. It describes the mechanism of how Cre delivery activates the expression of a reporter gene in both neurons and astrocytes of the cortex without tissue damage. It mentions the applications of this approach which are beneficial to the transient introduction of proteins into cells in vivo.
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- 2022
- Full Text
- View/download PDF
46. Basic principles of neuroimmunology.
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Yoshida, Tomomi M., Wang, Andrew, and Hafler, David A.
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NEUROIMMUNOLOGY , *CEREBROSPINAL fluid , *CENTRAL nervous system , *LYMPHATICS , *IMMUNE response , *CENTRAL nervous system physiology , *CEREBROSPINAL fluid examination , *MICROGLIA - Abstract
The brain is an immune-privileged organ such that immune cell infiltration is highly regulated and better tolerating the introduction of antigen to reduce risk of harmful inflammation. Thus, the composition and the nature of the immune response is fundamentally different in the brain where avoiding immunopathology is prioritized compared to other peripheral organs. While the principle of immune privilege in the central nervous system (CNS) still holds true, the role of the immune system in the CNS has been revisited over the recent years. This redefining of immune privilege in the brain is a result of the recent re-discovery of the extensive CNS meningeal lymphatic system and the identification of resident T cells in the brain, meningeal layers, and its surrounding cerebrospinal fluid (CSF) in both humans and rodents. While neuro-immune interactions have been classically studied in the context of neuroinflammatory disease, recent works have also elucidated unconventional roles of immune-derived cytokines in neurological function, highlighting the many implications and potential of neuro-immune interactions. As a result, the study of neuro-immune interactions is becoming increasingly important in understanding both CNS homeostasis and disease. Here, we review the anatomically distinct immune compartments within the brain, the known mechanisms of leukocyte trafficking and infiltration into the CNS and unique transcriptional and functional characteristics of CNS-resident immune cells. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
47. Acyloxyacyl hydrolase regulates microglia-mediated pelvic pain.
- Author
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Rahman-Enyart, Afrida, Yaggie, Ryan E., Bollinger, Justin L., Arvanitis, Constadina, Winter, Deborah R., Schaeffer, Anthony J., and Klumpp, David J.
- Subjects
- *
MICROGLIA , *PELVIC pain , *INTERSTITIAL cystitis , *CENTRAL nervous system , *PARAVENTRICULAR nucleus , *TOLL-like receptors , *CENTRAL nervous system physiology - Abstract
Chronic pelvic pain conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) remain clinical and mechanistic enigmas. Microglia are resident immune cells of the central nervous system (CNS) that respond to changes in the gut microbiome, and studies have linked microglial activation to acute and chronic pain in a variety of models, including pelvic pain. We have previously reported that mice deficient for the lipase acyloxyacyl hydrolase (AOAH) develop pelvic allodynia and exhibit symptoms, comorbidities, and gut dysbiosis mimicking IC/BPS. Here, we assessed the role of AOAH in microglial activation and pelvic pain. RNAseq analyses using the ARCHS4 database and confocal microscopy revealed that AOAH is highly expressed in wild type microglia but at low levels in astrocytes, suggesting a functional role for AOAH in microglia. Pharmacologic ablation of CNS microglia with PLX5622 resulted in decreased pelvic allodynia in AOAH-deficient mice and resurgence of pelvic pain upon drug washout. Skeletal analyses revealed that AOAH-deficient mice have an activated microglia morphology in the medial prefrontal cortex and paraventricular nucleus, brain regions associated with pain modulation. Because microglia express Toll-like receptors and respond to microbial components, we also examine the potential role of dysbiosis in microglial activation. Consistent with our hypothesis of microglia activation by leakage of gut microbes, we observed increased serum endotoxins in AOAH-deficient mice and increased activation of cultured BV2 microglial cells by stool of AOAH-deficient mice. Together, these findings demonstrate a role for AOAH in microglial modulation of pelvic pain and thus identify a novel therapeutic target for IC/BPS. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
48. Type 2 Diabetes Mellitus (T2DM) and Carbohydrate Metabolism in Relation to T2DM from Endocrinology, Neurophysiology, Molecular Biology, and Biochemistry Perspectives.
- Author
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Mills, Hilla, Acquah, Ronald, Tang, Nova, Cheung, Luke, Klenk, Susanne, Glassen, Ronald, Pirson, Magali, Albert, Alain, Hoang, Duong Trinh, and Van, Thang Nguyen
- Subjects
- *
CENTRAL nervous system physiology , *ENDOCRINOLOGY , *BIOCHEMISTRY , *HOMEOSTASIS , *CARBOHYDRATE metabolism , *NEUROPHYSIOLOGY , *METABOLISM , *TYPE 2 diabetes , *MOLECULAR biology - Abstract
Type 2 diabetes mellitus (T2DM) is a severe disease caused by metabolic disorders, particularly carbohydrate metabolism disorders. The disease is a fatal global trouble characterised by high prevalence rates, causing death, blindness, kidney failure, myocardial infarction, amputation of lower limps, and stroke. Biochemical metabolic pathways like glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis are critical pathways that regulate blood glucose levels with the glucokinase (GK) enzyme playing a central role in glucose homeostasis. Any factor that perturbs the aforementioned biochemical pathways is detrimental. Endocrinological, neurophysiological, and molecular biological pathways that are linked to carbohydrate metabolism should be studied, grasped, and manipulated in order to alleviate T2DM global chaos. The challenge, howbeit, is that, since the body is an integration of systems that complement one another, studying one "isolated" system is not very useful. This paper serves to discuss endocrinology, neurophysiology, and molecular biology pathways that are involved in carbohydrate metabolism in relation to T2DM. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
49. look on food intake and satiety: from humans to rodent models.
- Author
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Costa, Daniela G, Almeida, Cláudia, Cavadas, Cláudia, and Carmo-Silva, Sara
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CENTRAL nervous system physiology , *HYPOTHALAMUS physiology , *BIOLOGICAL models , *FOOD habits , *HOMEOSTASIS , *LEPTIN , *GLUCAGON-like peptide 1 , *SATISFACTION , *NUTRITIONAL requirements , *PROTEIN precursors , *INSULIN , *GLUCAGON , *DIETARY carbohydrates , *CHOLECYSTOKININ , *PEPTIDES , *DIETARY proteins , *LIPIDS - Abstract
Satiety is a complex state, influenced by numerous factors that go beyond food ingestion. Satiety influences food habits and behavior, thus affecting human health. This review provides an overview of physiological mechanisms involved in satiety and of methodologies to assess food intake and satiety in both animal models and humans. The following topics are highlighted: differences between satiety and satiation; how the central nervous system regulates food intake and satiety; the impact of different macronutrients on satiety; and how the manipulation of food composition might influence overall satiety. Bringing together knowledge on this myriad of satiety mechanisms and how we can study them is useful to better understand and control obesity and other eating disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
50. Neuromodulator hydrogen sulfide attenuates sickness behavior induced by lipopolysaccharide.
- Author
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Oliveira, Merelym K., Batista, Tatiane H., Rojas, Viviana Carolina T., Vitor-Vieira, Fernando, Reis, Letícia, Giusti, Fabiana Cardoso Vilela, and Giusti-Paiva, Alexandre
- Subjects
- *
HYDROGEN sulfide , *CENTRAL nervous system physiology , *LIPOPOLYSACCHARIDES , *LABORATORY rats - Abstract
Sickness behavior reflects a state of altered physiology and central nervous system function that occurs during systemic infection or inflammation, serving as an adaptive response to illness. This study aims to elucidate the role of hydrogen sulfide (H 2 S) in regulating sickness behavior and neuroinflammatory responses in a rat model of systemic inflammation. Adult male Wistar rats were treated with lipopolysaccharide (LPS) to induce sickness behavior. Intracerebroventricular (i.c.v.) pretreatments included aminooxyacetic acid (AOAA), an inhibitor of H 2 S synthesis, and sodium sulfide (NaHS), an H 2 S donor. Behavioral assays were conducted, along with the assessment of astrocyte activation, as indicated by GFAP expression in the hypothalamus. Pretreatment with NaHS mitigated LPS-induced behavioral changes, including hypophagia, social and exploratory deficits, without affecting peripheral cytokine levels, indicating a central modulatory effect. AOAA, conversely, accentuated certain behavioral responses, suggesting a complex role of endogenous H 2 S in sickness behavior. These findings were reinforced by a lack of effect on plasma interleukin levels but significant reduction in GFAP expression. Our findings support the central role of H 2 S in modulating neuroinflammation and sickness behavior, highlighting the therapeutic potential of targeting H 2 S signaling in neuroinflammatory conditions. • Hydrogen sulfide eases behavioral impact of lipopolysaccharide in rats. • NaHS counters LPS-induced behavioral changes effectively in rodent models. • AOAA enhances LPS-induced hypophagia, pointing to complex H2S roles. • H2S demonstrates significant neuroprotective actions against LPS in CNS. • NaHS icv use shows no change in cytokine levels LPS-induced, indicating central action. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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