Search

Early life stress (ELS), characterized as abuse, neglect, and abandonment, can cause several adverse consequences in the lives of affected individuals. ELS experiences can affect an individual's development in variable ways, persisting in the long term and promoting lasting impacts, considering that early exposure to stressors can be biologically incorporated, as prolonged stimulation of stress response systems affects the development of the brain structure and other body systems, increasing the risk of diseases associated with stress and cognitive impairment. This type of stress increases the risk of developing major depressive disorder (MDD) in a severe form that does not respond adequately to traditional antidepressant treatments. Several alterations are studied as mechanisms that relate ELS with MDD, such as epigenetic alterations, neurotransmitters, and neuronal signaling. This review discusses research that brings evidence about the ELS mechanisms involved in synaptic impairments and MDD. The processes involved in epigenetic changes and the HPA axis are highlighted, as well as changes in neurotransmitters and neuronal signaling mechanisms. [ABSTRACT FROM AUTHOR]

Previous neuroimaging research has established associations between urban exposure during early life and alterations in brain function and structure. However, the molecular mechanisms and behavioral relevance of these associations remain largely unknown. Here, we aimed to address this question using a combined analysis of multimodal data. Initially, we calculated amplitude of low-frequency fluctuations (ALFF) and gray matter volume (GMV) using resting-state functional and structural MRI to investigate their associations with early-life urbanization in a large sample of 511 healthy young adults. Then, we examined the spatial relationships of the identified neural correlates of early-life urbanization with gene expression, neurotransmitter, and behavioral domain atlases. Results showed that higher early-life urbanization scores were correlated with increased ALFF of the right fusiform gyrus and decreased GMV of the left dorsal medial prefrontal cortex and left precuneus. Remarkably, the identified neural correlates of early-life urbanization were spatially correlated with expression of gene categories primarily involving immune system process, signal transduction, and cellular metabolic process. Concurrently, there were significant associations between the neural correlates and specific neurotransmitter systems including dopamine, acetylcholine, and serotonin. Finally, we found that the ALFF correlates were associated with behavioral terms including "perception," "sensory," "cognitive control," and "reasoning." Apart from expanding existing knowledge of early-life urban environmental risk for mental disorders and health in general, our findings may contribute to an emerging framework for integrating social science, neuroscience, genetics, and public policy to respond to the major health challenge of world urbanization. [ABSTRACT FROM AUTHOR]

The betel nut is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. Arecoline is an active ingredient from the areca nut. It has many pharmacological effects and can affect the central nervous system. In this study, we found that arecoline can relieve fatigue behavior. Objective: This research aims to estimate the anti-fatigue effects of arecoline and explore its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL/6 mice were randomly assigned to six groups: a control group, an SD-induced fatigue model group, a group that received Rhodiola Rosea capsules (2.5 mg/kg), and three arecoline groups, which were administered at low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on mouse fatigue-related behaviors were assessed by behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. The release levels of the related biochemical markers were measured by enzyme-linked immunosorbent assays (ELISAs). Western blotting was employed to quantify the expression levels of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline obviously decreased both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased the contents of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol in the serum, while it elevated the levels of total testosterone, lactate dehydrogenase, and immunoglobulin G. Furthermore, it significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels showed significant increases, cytokine levels were markedly reduced, and the expressions of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissues were significantly upregulated. Conclusions: This study demonstrates that arecoline has anti-fatigue activity, and the specific mechanisms are associated with elevating glucose and lipid metabolism levels, relieving oxidative stress damage, inhibiting neuroinflammatory response, and regulating neurotransmitter levels and the Keap1/Nrf2/HO-1 signaling pathway. The research provides a new direction for arecoline's potential in preventing and improving fatigue. [ABSTRACT FROM AUTHOR]

Objective To study the sedative and hypnotic effects of Yening Capsules and investigate its bioactive mechanism in mice. Methods The mice were randomly divided into control group, estazolam group (0.8 mg/kg）, low, medium and high-dose Yening Capsules groups (400, 600 and 800 mg/kg) . The locomotor activity, latency to persistent sleep, sleep duration and sleep rate were determined respectively in mice via the open field test and injection of pentobarbital sodium in subthreshold and suprathreshold doses. The content of GABA, 5-HT, DA and NE in brain tissue of mice were detected by enzymelinked immunosorbent assay（ELISA）. Results Compared with the control group, Yening Capsules medium and high dose group (P<0.05, P<0.01）significantly decreased the locomotor activity of mice.The sleep latency in Yening Capsules medium and high dose group were significantly shorten (P<0.05, P<0.05）and the sleep duration (P<0.05, P<0.01）were extended. The sleep rate of Yening Capsules medium and high dose groups (P<0.05, P<0.01) was significantly increased. Compared with the control group, high dose of Yening Capsules can significantly increase GABA (P<0.05), 5-HT (P<0.05), DA (P<0.05), NE (P<0.01) in mouse brain tissue. Conclusion Yening Capsules had obvious sedative and hypnotic effects, and its mechanism may be related to the increasement of GABA, 5-HT, DA and NE level in brain tissue of mice. [ABSTRACT FROM AUTHOR]

Synaptic plasticity, including long‐term potentiation (LTP) and long‐term depression (LTD), is an essential phenomenon in memory formation as well as maintenance along with many other cognitive functions, such as those needed for coping with external stimuli. Synaptic plasticity consists of gradual changes in the biochemistry and morphology of pre‐ and postsynaptic neurons, particularly in the hippocampus. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory‐related tasks. Evidence regarding the effects of cannabinoids on LTP and memory is contradictory. While cannabinoids can affect a variety of specific cannabinoid receptors (CBRs) and nonspecific receptors throughout the body and brain, they exert miscellaneous systemic and local cerebral effects. Given the increasing use of cannabis, mainly among the young population, plus its potential adverse long‐term effects on learning and memory processes, it could be a future global health challenge. Indeed, the impact of cannabinoids on memory is multifactorial and depends on the dosage, timing, formula, and route of consumption, plus the background complex interaction of the endocannabinoids system with other cerebral networks. Herein, we review how exogenously administrated organic cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters. Significance statement: Synaptic plasticity, including LTP and LTD, is an essential phenomenon in memory formation and maintenance, along with many other cognitive functions. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory‐related tasks. Cannabinoids can affect a variety of specific and nonspecific receptors throughout the body and brain, they exert anxiolytic, anti‐inflammatory, psychoactive, and cognitive effects. Given the increasing use of cannabis, mainly among the young population plus its potential adverse long‐term effects on learning and memory processes, it could be a future global health challenge. In this work, we review how exogenously administrated cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters. [ABSTRACT FROM AUTHOR]

[Display omitted] • Methamphetamine induces gene expression changes in microglia that vary by phase of self-administration (maintenance; forced abstinence). • Methamphetamine induces morphological changes in microglia consistent with activation. • These transcriptional and morphological changes persist for up to 21 days after final exposure to methamphetamine. • Transcriptional analysis suggests possible involvement of microglia in regulation of neurotransmitter signaling. • PLX5622 treatment ablates microglia and increases methamphetamine-taking. • PLX5622 treatment during 21-day forced abstinence does not affect context-induced methamphetamine-seeking. Methamphetamine use disorder (MUD) is a chronic, relapsing disease that is characterized by repeated drug use despite negative consequences and for which there are currently no FDA-approved cessation therapeutics. Repeated methamphetamine (METH) use induces long-term gene expression changes in brain regions associated with reward processing and drug-seeking behavior, and recent evidence suggests that methamphetamine-induced neuroinflammation may also shape behavioral and molecular responses to the drug. Microglia, the resident immune cells in the brain, are principal drivers of neuroinflammatory responses and contribute to the pathophysiology of substance use disorders. Here, we investigated transcriptional and morphological changes in dorsal striatal microglia in response to methamphetamine-taking and during methamphetamine abstinence, as well as their functional contribution to drug-taking behavior. We show that methamphetamine self-administration induces transcriptional changes associated with protein folding, mRNA processing, immune signaling, and neurotransmission in dorsal striatal microglia. Importantly, many of these transcriptional changes persist through abstinence, a finding supported by morphological analyses. Functionally, we report that microglial ablation increases methamphetamine-taking, possibly involving neuroimmune and neurotransmitter regulation. In contrast, microglial depletion during abstinence does not alter methamphetamine-seeking. Taken together, these results suggest that methamphetamine induces both short and long-term changes in dorsal striatal microglia that contribute to altered drug-taking behavior and may provide valuable insights into the pathophysiology of MUD. [ABSTRACT FROM AUTHOR]

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research. [ABSTRACT FROM AUTHOR]

Human stem cells and derivatives transplantation are widely used to treat nervous system diseases, while the fate determination of transplanted cells is not well elucidated. To explore cell fate changes of human brain organoids before and after transplantation, human brain organoids are transplanted into prefrontal cortex (PFC) and hippocampus (HIP), respectively. Single‐cell sequencing is then performed. According to time‐series sample comparison, transplanted cells mainly undergo neural development at 2 months post‐transplantation (MPT) and then glial development at 4MPT, respectively. A different brain region sample comparison shows that organoids grafted to PFC have obtained cell fate close to those of host cells in PFC, other than HIP, which may be regulated by the abundant expression of dopamine (DA) and acetylcholine (Ach) in PFC. Meanwhile, morphological complexity of human astrocyte grafts is greater in PFC than in HIP. DA and Ach both activate the calcium activity and increase morphological complexity of astrocytes in vitro. This study demonstrates that human brain organoids receive host niche factor regulation after transplantation, resulting in the alignment of grafted cell fate with implanted brain regions, which may contribute to a better understanding of cell transplantation and regenerative medicine. [ABSTRACT FROM AUTHOR]

Mass spectrometry imaging (MSI) platforms such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) are advantageous for a variety of applications, including elucidating the localization of neurotransmitters (NTs) and related molecules with respect to ion abundance across a sample without the need for derivatization or organic matrix application. While IR-MALDESI-MSI conventionally uses a thin exogenous ice matrix to improve signal abundance, it has been previously determined that sucrose embedding without the ice matrix improves detection of lipid species in striatal, coronal mouse brain sections. This work considers components of this workflow to determine the optimal sample preparation and matrix to enhance the detection of NTs and their related metabolites in coronal sections from the striatal region of the mouse brain. The discoveries herein will enable more comprehensive follow-on studies for the investigation of NTs to enrich biological pathways and interpretation related to neurodegenerative diseases and ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: The annual incidence of insomnia continues to increase owing to changes in lifestyle habits, increased work pressure, and increased environmental pollution. In recent years, an increasing number of external therapies have been proven effective in treating insomnia and have been widely used. However, the relative benefits and harms of external therapies remain uncertain, and an optimal treatment strategy has not yet been determined. Objectives: A network meta-analysis was performed to evaluate and compare the efficacy and safety of multiple external therapies for patients with insomnia. Methods: Eight electronic databases were comprehensively searched from their inception to June 2023 for relevant literature. We also searched the grey literature and reviewed the reference lists of related systematic reviews. Two independent reviewers performed the study selection, data extraction, and bias assessment of the included randomized controlled trials (RCTs) using the Cochrane Reviewers' Handbook, and a network meta-analysis was conducted using Stata and RevMan software. Results: In total, 14,826 studies were identified. Of these, 83 studies, including 9 external therapies and 6,100 patients, were deemed eligible for the present network meta-analysis. Except for the SL outcome, each external therapy was better than conventional medicine and the sham intervention (SI) in improving sleep quality. In terms of improving the psychological state indices of insomnia patients, each external therapy was superior to the SI; each external therapy had a better effect on the regulation of monoamine neurotransmitters. Tuina may be the most effective intervention in improving the total effective rate, Pittsburgh sleep quality index score, and SL. Repetitive transcranial magnetic stimulation (rTMS) perhaps resulted in the best improvement in total sleep time and awakening time (surface under the cumulative ranking curve [SUCRA] = 78.3 and 75.4%, respectively); and moxibustion (MB) and hyperbaric oxygen (HBO) were the most effective in reducing Self-rating Anxiety Scale and Self-rating Depression Scale scores. In terms of improving the monoamine neurotransmitters 5-hydroxytryptamine, norepinephrine, and dopamine, the best interventions were acupoint catgut embedding, electroacupuncture, and Tuina (SUCRA = 82.0, 69.9 and 90.3%, respectively). Safety results showed that the three safest interventions were the SI, Tuina, and foot bath. No serious adverse events were reported across the studies, and the most common minor adverse events included drowsiness, pain, excessive thirst, and hematoma. Conclusion: Both Tuina and rTMS have significant effects on improving sleep quality, but the safety of rTMS is low. Therefore, Tuina can be recommended as the first line of treatment to improve sleep quality. If a patient's anxiety and depression symptoms are evident, MB or HBO can be selected for treatment based on the actual situation. External therapy to improve sleep quality may be related to the regulation of monoamine neurotransmitters, which may be a potential mechanism of action. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and interest restricted to specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 h post-fertilization, rearing them to the adult stage in fish water. For the first time, an integrative approach combining behavioral analysis and neurotransmitters profile has been used for determining the effects of early-life exposure to VPA both in the larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. A neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the potential predictive validity of this model for ASD research. [ABSTRACT FROM AUTHOR]

Introduction: Sleep loss and sleep deprivation (SD) cause deleterious influences on health, cognition, mood and behaviour. Nevertheless, insufficient sleep and SD are prevalent across many industries and occur in various emergencies. The deleterious consequences of SD have yet to be fully elucidated. This study aimed to assess the extensive influences of SD on physiology, vigilance, and plasma biochemical variables. Methods: Seventeen volunteers were recruited to participate in a 32.5-h SD experiment. Multiple physiological and cognitive variables, including tympanic temperature, blood oxygen saturation (SaO2), and vigilance were recorded. Urinal/salivary samples were collected and subjected to cortisol or cortisone analysis, and plasma samples were subjected to transcriptomic analysis of circular RNA (circRNA) expression using microarray. Plasma neurotransmitters were measured by targeted metabolic analysis, and the levels of inflammatory factors were assessed by antibody microarray. Results: The volunteers showed significantly increased sleepiness and decreased vigilance during SD, and the changes in circadian rhythm and plasma biochemistry were observed. The plasma calcium (p = 0.0007) was induced by SD, while ischaemia-modified albumin (IMA, p = 0.0030) and total bile acid (TBA, p = 0.0157) decreased. Differentially expressed circRNAs in plasma were identified, which are involved in multiple signaling pathways including neuronal regulation and immunity. Accordingly, SD induced a decrease in 3-hydroxybutyric acid (3OBH, p = 0.0002) and an increase in thyroxine (T4, p < 0.0001) in plasma. The plasma anti-inflammatory cytokine IL-10 was downregulated while other ten inflammatory factors were upregulated. Conclusion: This study demonstrates that SD influences biochemical, physiological, cognitive variables, and the significantly changed variables may serve as candidates of SD markers. These findings may further our understanding of the detrimental consequence of sleep disturbance at multiple levels. [ABSTRACT FROM AUTHOR]

The present study reported the synthesis of three CuX/S-doped g-C3N4 nanocomposites (CuX= CuO/CuS/Cu2O) via an efficient and simple approach. The various prepared nanocomposites were characterized with different characterization techniques and demonstrated the synthesis of pure nanocomposites. Among three CuX/S-doped g-C3N4 nanocomposites, CuS/S-doped g-C3N4 exhibits a remarkable electrochemical performance for detecting dopamine (DA). Herein, various electrochemical parameters, such as the volume of the electrocatalyst used and the solution's pH, were optimized to achieve efficient detection. Under favorable conditions, CuS/S-doped g-C3N4 demonstrated an effective electrochemical response for DA detection using linear sweep voltammetry (LSV) and cyclic voltammetry (CV) methods. The proposed sensor afforded a linear plot between the anodic peak current and concentration of DA in the range of 0–200 μM with the low limit of detection (0.1227 μM or 122.7 nM) between the concentration of DA and anodic peak current. In addition, the constructed sensor for DA detection displayed satisfactory stability and reproducibility. The real sample, i.e., human serum, was employed to assess the ability to perform real-time analysis of the sensing platform. The developed sensor displayed a favorable recovery rate, illustrating its practical functionality. [ABSTRACT FROM AUTHOR]

Previous researches of tobacco use disorder (TUD) has overlooked the hierarchy of cortical functions and single modality design separated the relationship between macroscopic neuroimaging aberrance and microscopic molecular basis. At present, intrinsic timescale gradient of TUD and its molecular features are not fully understood. Our study recruited 146 male subjects, including 44 heavy smokers, 50 light smokers and 52 non-smokers, then obtained their rs-fMRI data and clinical scales related to smoking. Intrinsic neural timescale (INT) method was performed to describe how long neural information was stored in a brain region by calculating the autocorrelation function (ACF) of each voxel to examine the difference in the ability of information integration among the three groups. Then, correlation analyses were conducted to explore the relationship between INT abnormalities and clinical scales of smokers. Finally, cross-modal JuSpace toolbox was used to investigate the association between INT aberrance and the expression of specific receptor/transporters. Compared to healthy controls, TUD subjects displayed decreased INT in control network (CN), default mode network (DMN), sensorimotor areas and visual cortex, and such trend of decreasing INT was more pronounced in heavy smokers. Moreover, various neurotransmitters (including dopaminergic, acetylcholine and μ-opioid receptors) were involved in the molecular mechanism of timescale decreasing and differed in heavy and light smokers. These findings supplied novel insights into the brain functional aberrance in TUD from an intrinsic neural dynamic perspective and confirm INT was a potential neurobiological marker. And also established the connection between macroscopic imaging aberrance and microscopic molecular changes in TUD. [ABSTRACT FROM AUTHOR]

During the last few decades, identifying the physiological pathways involved in appetite regulation has become popular among researchers. Although studying feeding regulation in birds, especially in poultry (for breeding purposes) and ornamental birds (for therapeutic purposes), is extremely important, limited experiments have been conducted on these animal models. Until today, more than 50 neurotransmitters affecting birds' appetite have been identified. In the current study, we overviewed the role of one of the most important neural mediators, neuropeptide Y (NPY), in regulating avian appetite. Based on the findings, the presence of this neuropeptide and its receptors in the key areas of food intake regulation, especially the hypothalamus's arcuate nucleus (ARC), has been proven. Numerous studies on birds have repeatedly shown the hyperphagic effects of NPY. Among the different NPY receptors, type 1, 2, and 5 receptors play the most important role in appetite regulation. It has also been observed that the interaction of NPY with neurotransmitters such as glucagon-like peptide-1 (GLP1), vasotocin, bombesin, opioids, alpha-melanocyte-stimulating hormone (α-MSH), cocaine- and amphetamine-regulated transcript (CART) and gamma aminobutyric acid (GABA) is effective in NPY-induced hyperphagia. In addition, the NPY system is also involved in the effects of various mediators such as adiponectin, neuropeptide W (NPW), phoenixin-14, visfatin, adrenomedullin, spexin, kisspeptin, insulin, and somatostatin on appetite regulation. Finally, NPY seems to be one of the most important appetite-stimulating factors in birds and also plays an undeniable role in the effects of other neurotransmitters on appetite regulation. [ABSTRACT FROM AUTHOR]

The onset of depression commonly occurs in adolescence; therefore, depressive prevention and intervention are pivotal during this period. It is becoming evident that neurotransmitter imbalance and gut microbiota dysbiosis are prominent causes of depression. However, the underlying links and mechanisms remain poorly understood. In this study, with 16S ribosomal RNA gene sequencing, genus Coprococcus markedly differentiated between the healthy and unmedicated depressive adolescents. Based on this, transplantation of Coprococcus eutactus (C.e.) was found to dramatically ameliorate the chronic restraint stress (CRS) induced depression-like changes and prevent synaptic loss and glial-stimulated neuroinflammation in mice. The Ultra-high performance liquid chromatography tandem mass spectrometry analysis (UHPLC-MS/MS) further showed that neurotoxic neurotransmitters in kynurenine pathway (KP) such as 3-hydroxykynurenine (3−HK) and 3-hydroxyanthranilic acid (3-HAA) decreased in mouse brains, mechanistically deciphering the transfer of the tryptophan metabolic pathway to serotonin metabolic signaling in the brain after C.e. treatment, which was also verified in the colon. Molecularly, blockage of KP activities mediated by C.e. was ascribed to the restraint of the limit-step enzymes responsible for kynurenine, 3-HK, and quinolinic acid generation. In the colon, C.e. treatment significantly recovered goblet cells and mucus secretion in CRS mice which may ascribe to the rebalance of the disordered gut microbiota, especially Akkermansia , Roseburia , Rikenella , Blautia , and Alloprevotella. Taken together, the current study reveals for the first time the beneficial effects and potential mechanisms of C.e. in ameliorating CRS-induced depression, unraveling the direct links between C.e. treatment and neurotransmitter rebalance, which may provide efficacious therapeutic avenues for adolescent depressive intervention. [Display omitted] • Depression-like behaviors attenuated by administrating Coprococcus eutactus (C.e.). • C.e. improved neurotransmitter metabolism in CRS mice. • C.e. regulates tryptophan metabolism rate-limiting enzyme and reconstructed the disordered gut microbiota. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non‐pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter‐related analyses. Wild‐type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aβ accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography–tandem mass spectrometry showed that EE enhanced synapse‐ and neurotransmitter‐related networks and upregulated synapse‐ and neurotransmitter‐related proteins in the AD brain. Furthermore, neurotransmitter‐related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse‐related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a common neurological disease with recognition ability loss symptoms and a major contributor to dementia cases worldwide. Gastrodia elata Bl. (GE), a food of medicine–food homology, has been reported to have a mitigating effect on memory and learning ability decline. However, the effect of GE fermented by Lactobacillus plantarum, Acetobacter pasteurianus, and Saccharomyces (FGE) on alleviating cognitive deficits in AD was not studied. Mice were randomly divided into six groups, control, model, donepezil, low, medium, and high doses of FGE, and D‑Galactose/Aluminum chloride (D‑Gal/AlCl3) was used to establish an AD‑like mouse model. The results indicated that FGE could improve the production of neurotransmitters and relieve oxidative stress damage in AD‑like mice, which was evidenced by the declined levels of amyloid‑β (Aβ), Tau, P‑Tau, acetylcholinesterase (AchE), and malondialdehyde (MDA), and increased acetylcholine (Ach), choline acetyltransferase (ChAT), and superoxide dismutase (SOD) levels in brain tissue. Notably, FGE could enhance the richness of the gut microbiota, especially for beneficial bacteria such as Lachnospira and Lactobacillus. Non‑target metabolomics results indicated that FGE could affect neurotransmitter levels by regulating amino acid metabolic pathways to improve AD symptoms. The FGE possessed an ameliorative effect on AD by regulating neurotransmitters, oxidative stress levels, and gut microbiota and could be considered a good candidate for ameliorating AD. [ABSTRACT FROM AUTHOR]

Over the past decades, emerging evidence in the literature has demonstrated that the innervation of bone is a crucial modulator for skeletal physiology and pathophysiology. The nerve‐bone axis sparked extensive preclinical and clinical investigations aimed at elucidating the contribution of nerve‐bone crosstalks to skeleton metabolism, homeostasis, and injury repair through the perspective of skeletal neurobiology. To date, peripheral nerves have been widely reported to mediate bone growth and development and fracture healing via the secretion of neurotransmitters, neuropeptides, axon guidance factors, and neurotrophins. Relevant studies have further identified several critical neural pathways that stimulate profound alterations in bone cell biology, revealing a complex interplay between the skeleton and nerve systems. In addition, inspired by nerve‐bone crosstalk, novel drug delivery systems and bioactive materials have been developed to emulate and facilitate the process of natural bone repair through neuromodulation, eventually boosting osteogenesis for ideal skeletal tissue regeneration. Overall, this work aims to review the novel research findings that contribute to deepening the current understanding of the nerve‐bone axis, bringing forth some schemas that can be translated into the clinical scenario to highlight the critical roles of neuromodulation in the skeletal system. [ABSTRACT FROM AUTHOR]

Dopamine (DA), ascorbic acid (AA), and uric acid (UA) are crucial neurochemicals, and their abnormal levels are involved in various neurological disorders. While electrodes for their detection have been developed, achieving the sensitivity required for in vivo applications remains a challenge. In this study, we proposed a synthetic Au24Cd nanoenzyme (ACNE) that significantly enhanced the electrochemical performance of metal electrodes. ACNE-modified electrodes demonstrated a remarkable 10-fold reduction in impedance compared to silver microelectrodes. Furthermore, we validated their excellent electrocatalytic activity and sensitivity using five electrochemical detection methods, including cyclic voltammetry, differential pulse voltammetry, square-wave pulse voltammetry, normal pulse voltammetry, and linear scanning voltammetry. Importantly, the stability of gold microelectrodes (Au MEs) modified with ACNEs was significantly improved, exhibiting a 30-fold enhancement compared to Au MEs. This improved performance suggests that ACNE functionalization holds great promise for developing micro-biosensors with enhanced sensitivity and stability for detecting small molecules. [ABSTRACT FROM AUTHOR]

Genetically encoded optical sensors and advancements in microscopy instrumentation and techniques have revolutionized the scientific toolbox available for probing complex biological processes such as release of specific neurotransmitters. Most genetically encoded optical sensors currently used are based on fluorescence and have been highly successful tools for single-cell imaging in superficial brain regions. However, there remains a need to develop new tools for reporting neuronal activity in vivo within deeper structures without the need for hardware such as lenses or fibers to be implanted within the brain. Our approach to this problem is to replace the fluorescent elements of the existing biosensors with bioluminescent elements. This eliminates the need of external light sources to illuminate the sensor, thus allowing deeper brain regions to be imaged noninvasively. Here, we report the development of the first genetically encoded neurotransmitter indicators based on bioluminescent light emission. These probes were optimized by high-throughput screening of linker libraries. The selected probes exhibit robust changes in light output in response to the extracellular presence of the excitatory neurotransmitter glutamate. We expect this new approach to neurotransmitter indicator design to enable the engineering of specific bioluminescent probes for multiple additional neurotransmitters in the future, ultimately allowing neuroscientists to monitor activity associated with a specific neurotransmitter as it relates to behavior in a variety of neuronal and psychiatric disorders, among many other applications.

Psychiatric disorders exhibit a shared neuropathology, yet the diverse presentations among patients necessitate the identification of transdiagnostic subtypes to enhance diagnostic and treatment strategies. This study aims to unveil potential transdiagnostic subtypes based on personalized gray matter morphological abnormalities. A total of 496 patients with psychiatric disorders and 255 healthy controls (HCs) from three distinct datasets (one for discovery and two for validation) were enrolled. Individualized gray matter morphological abnormalities were determined using normative modeling to identify transdiagnostic subtypes. In the discovery dataset, two transdiagnostic subtypes with contrasting patterns of structural abnormalities compared to HCs were identified. Reproducibility and generalizability analyses demonstrated that these subtypes could be generalized to new patients and even to new disorders in the validation datasets. These subtypes were characterized by distinct disease epicenters. The gray matter abnormal pattern in subtype 1 was mainly linked to excitatory receptors, whereas subtype 2 showed a predominant association with inhibitory receptors. Furthermore, we observed that the gray matter abnormal pattern in subtype 2 was correlated with transcriptional profiles of inflammation-related genes, while subtype 1 did not show this association. Our findings reveal two robust transdiagnostic biotypes, offering novel insights into psychiatric nosology. • We identify two robust transdiagnostic subtypes based on individualized gray matter morphological abnormalities. • These subtypes exhibiting contrasting patterns of structural abnormalities relative to healthy controls. • The identified subtypes are validated using independent datasets and can be extended to unseen disorders. [ABSTRACT FROM AUTHOR]

Abstract A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology. With the discovery of abnormally elevated inflammation in menopausal depressed women, immune imbalance has become a novel focus in the study of menopausal depression. In this paper, we examined the characteristics and possible mechanisms of immune imbalance caused by decreased estrogen levels during menopause and found that estrogen deficiency disrupted immune homeostasis, especially the levels of inflammatory cytokines through the ERα/ERβ/GPER-associated NLRP3/NF-κB signaling pathways. We also analyzed the destruction of the blood-brain barrier, dysfunction of neurotransmitters, blockade of BDNF synthesis, and attenuation of neuroplasticity caused by inflammatory cytokine activity, and investigated estrogen-immuno-neuromodulation disorders in menopausal depression. Current research suggests that drugs targeting inflammatory cytokines and NLRP3/NF-κB signaling molecules are promising for restoring homeostasis of the estrogen-immuno-neuromodulation system and may play a positive role in the intervention and treatment of menopausal depression.

Summary: Objectives: Pyridoxal 5ʹ-phosphate (PLP) is an active and major form of vitamin B6 (VB6) in the body. PLP is essential as a cofactor for many enzymes involved in amino acid metabolism, and VB6 deficiency is associated with neurological disorders, such as epileptic-like symptoms, depression and confusion. However, the link between neuronal dysfunction and VB6 deficiency is unclear. In this study, we investigated how neuronal cells are affected by low cellular PLP levels using the neuroblastoma SH-SY5Y cell line. Methods: SH-SY5Y cells were cultured in pyridoxine-free medium supplemented with 10% fetal bovine serum and cell viability, intracellular PLP concentration, and metabolites were evaluated. Pyridoxine-free medium supplemented with 10% FBS contained 3 nM of PLP derived from FBS. Media containing various concentration of PLP were prepared using pyridoxine-free medium. Additionally, reactive oxygen species level and cell viability were assessed when cells were treated with 100 μM of hydrogen peroxide in media containing different concentrations of PLP. Results: SH-SY5Y cells had a decreased intracellular PLP level of 38 pmol/mg protein but proliferated when cells were cultured in the PLP-non-added medium. Metabolome analysis revealed the levels of neurotransmitters such as dopamine, norepinephrine, and 4-aminobutyric acid were decreased in cells cultured in the PLP-non-added medium compared with the PLP-added medium. The concentration of glutathione, an antioxidant, was also reduced. Furthermore, when cells were cultured in the PLP-non-added medium, hydrogen peroxide treatment reduced cell viability and increased intracellular reactive oxygen species levels in a concentration-dependent manner. These findings show that a growth environment low in VB6 decreases cellular glutathione and reduces resistance to oxidative stress. Conclusions: Overall, these findings show that low VB6 not only reduces neurotransmitter production, but also reduces glutathione levels, rendering cells more susceptible to oxidative stress and increasing the risk of neurodegenerative changes.

A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology. With the discovery of abnormally elevated inflammation in menopausal depressed women, immune imbalance has become a novel focus in the study of menopausal depression. In this paper, we examined the characteristics and possible mechanisms of immune imbalance caused by decreased estrogen levels during menopause and found that estrogen deficiency disrupted immune homeostasis, especially the levels of inflammatory cytokines through the ERα/ERβ/GPER-associated NLRP3/NF-κB signaling pathways. We also analyzed the destruction of the blood-brain barrier, dysfunction of neurotransmitters, blockade of BDNF synthesis, and attenuation of neuroplasticity caused by inflammatory cytokine activity, and investigated estrogen-immuno-neuromodulation disorders in menopausal depression. Current research suggests that drugs targeting inflammatory cytokines and NLRP3/NF-κB signaling molecules are promising for restoring homeostasis of the estrogen-immuno-neuromodulation system and may play a positive role in the intervention and treatment of menopausal depression. [ABSTRACT FROM AUTHOR]

General anesthetics disrupt brain network dynamics through multiple pathways, in part through postsynaptic potentiation of inhibitory ion channels as well as presynaptic inhibition of neuroexocytosis. Common clinical general anesthetic drugs, such as propofol and isoflurane, have been shown to interact and interfere with core components of the exocytic release machinery to cause impaired neurotransmitter release. Recent studies however suggest that these drugs do not affect all synapse subtypes equally. We investigated the role of the presynaptic release machinery in multiple neurotransmitter systems under isoflurane general anesthesia in the adult female Drosophila brain using live-cell super–resolution microscopy and optogenetic readouts of exocytosis and neural excitability. We activated neurotransmitter-specific mushroom body output neurons and imaged presynaptic function under isoflurane anesthesia. We found that isoflurane impaired synaptic release and presynaptic protein dynamics in excitatory cholinergic synapses. In contrast, isoflurane had little to no effect on inhibitory GABAergic or glutamatergic synapses. These results present a distinct inhibitory mechanism for general anesthesia, whereby neuroexocytosis is selectively impaired at excitatory synapses, while inhibitory synapses remain functional. This suggests a presynaptic inhibitory mechanism that complements the other inhibitory effects of these drugs. [ABSTRACT FROM AUTHOR]

The precise and effective detection of neurotransmitters (NTs) is crucial for clinical investigation of neuronal processes, and timely monitoring of NT‐related chronic diseases. However, sensitive detection of specific NT with unprecedented selectivity is highly challenging due to similarities in chemical and electronic structures of various interfering neurochemicals. Herein, an anionic conjugated polyelectrolyte Poly[(9,9‐bis(4’‐sulfonatobutyl)fluorene‐co‐alt‐1,4‐phenylene) sodium], PFPS was rationally designed and synthesized for amplified detection and point‐of‐care (PoC) determination of monoamine neurotransmitter, serotonin (5‐Hydroxy tryptamine or 5‐HT, also diagnostic biomarker of carcinoid tumor) in human blood plasma. The PFPS displayed a remarkable sensing response with an exceptionally high fluorescence quenching constant of 1.14×105 M−1 and an ultralow detection limit of 0.67 μM or 0.142 ppm, much below the clinical range. Furthermore, a smartphone‐enabled portable platform was constructed for real‐time onsite detection of 5‐HT by quantification of visual fluorescence response of PFPS into RGB values using a color recognizer android application. The smartphone platform could be readily applied for convenient, non‐invasive PoC testing of 5‐HT levels in complex biological fluids accurately and is expected to revolutionize clinical diagnosis and personalized health care devices. [ABSTRACT FROM AUTHOR]

The optic afferent nervous system (OANS) plays a significant role in generating vision and circadian behaviors based on light detection and signals from the endocrine system. However, the bionic simulation of this photochemically mediated behavior is still a challenge for neuromorphic devices. Herein, stimuli of neurotransmitters at ultralow concentrations and illumination are coupled to artificial synapses with the aid of biofunctionalized heterojunction and tunneling to successfully simulate a circadian neural response. Furthermore, the mechanisms underlying the photosensitive synaptic current in response to stimuli are described. Interestingly, this OANS is demonstrated to be capable of mimicking normal and abnormal circadian learnability by combining the measured synaptic current with a three‐layer spike neural network. Strong theoretical and experimental evidence, as well as applications, are provided for the proposed biomimetic OANS to demonstrate that it can reproduce biological circadian behavior, thus establishing it as a promising candidate for future neuromorphic intelligent robots. [ABSTRACT FROM AUTHOR]

Alcohol misuse is associated with altered punishment and reward processing. Here, we investigated neural network responses to reward and punishment and the molecular profiles of the connectivity features predicting alcohol use severity in young adults. We curated the Human Connectome Project data and employed connectome-based predictive modeling (CPM) to examine how functional connectivity (FC) features during wins and losses are associated with alcohol use severity, quantified by Semi-Structured Assessment for the Genetics of Alcoholism, in 981 young adults. We combined the CPM findings and the JuSpace toolbox to characterize the molecular profiles of the network connectivity features of alcohol use severity. The connectomics predicting alcohol use severity appeared specific, comprising less than 0.12% of all features, including medial frontal, motor/sensory, and cerebellum/brainstem networks during punishment processing and medial frontal, fronto-parietal, and motor/sensory networks during reward processing. Spatial correlation analyses showed that these networks were associated predominantly with serotonergic and GABAa signaling. To conclude, a distinct pattern of network connectivity predicted alcohol use severity in young adult drinkers. These "neural fingerprints" elucidate how alcohol misuse impacts the brain and provide evidence of new targets for future intervention. [ABSTRACT FROM AUTHOR]

The behaviors that characterize sleep have been observed across a broad range of different species. While much attention has been placed on vertebrates (mostly mammals and birds), the grand diversity of invertebrates has gone largely unexplored. Here, we introduce the intrigue and special value in the study of sleeping platyhelminth flatworms. Flatworms are closely related to annelids and mollusks, and yet are comparatively simple. They lack a circulatory system, respiratory system, endocrine glands, a coelom, and an anus. They retain a central and peripheral nervous system, various sensory systems, and an ability to learn. Flatworms sleep, like other animals, a state which is regulated by prior sleep/wake history and by the neurotransmitter GABA. Furthermore, they possess a remarkable ability to regenerate from a mere fragment of the original animal. The regenerative capabilities of flatworms make them a unique bilaterally symmetric animal to study a link between sleep and neurodevelopment. Lastly, the recent applications of tools for probing the flatworm genome, metabolism, and brain activity make their entrance into the field of sleep research all the more timely. [ABSTRACT FROM AUTHOR]

An analytical method for the simultaneous quantification of neurotransmitters has been developed using reversed-phase ion-pair high performance liquid chromatography (RPIP-HPLC) coupled with electrochemical detection (ECD). As a strategy to simultaneously analyze acetylcholine, glutamate, and γ-aminobutyric acid, which were previously difficult to analyze in ECD, along with serotonin and dopamine, the ion pair separation technique was optimized, and electroactivity was induced by eluting with strong alkaline solution. This method achieved improved sensitivity, showing limits of quantification of 0.02 to 0.1 μg/mL and linear regression coefficients of determination of 0.9938–0.9994 through the use of an 8% acetonitrile solution containing 15 mM H3PO4 and 0.4 mM sodium 1-octanesulfonate as the mobile phase and 200 mM NaOH as the post-column eluent, detected at the gold electrode. All inter- and intra-day precision were below 4.10%, and the average recoveries were 97.43–103.69%. In an application comparing cerebral cortical tissues and hippocampal tissues between a control group and a scopolamine-treated group, the levels of the five components showed a clear difference. As a result of evaluating the eco-friendliness of this method, the Analytical GREEnness metric was determined as 0.47. Our method is expected to be useful in screening for neurotransmitters in various biological and clinical samples. [ABSTRACT FROM AUTHOR]

An essential regulator of neurodegenerative conditions like Alzheimer's disease (AD) is the gut microbiota. Alterations in intestinal permeability brought on by gut microbiota dysregulation encourage neuroinflammation, central immune dysregulation, and peripheral immunological dysregulation in AD, as well as hasten aberrant protein aggregation and neuronal death in the brain. However, it is unclear how the gut microbiota transmits information to the brain and how it influences brain cognition and function. In this review, we summarized the multiple pathways involved in the gut microbiome in AD and provided detailed treatment strategies based on the gut microbiome. Based on these observations, this review also discusses the problems, challenges, and strategies to address current therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Smoking tobacco is a serious global health problem that is associated with psychiatric disorders and increased mortality rates. Nicotine, the main compound consumed during smoking, causes damage to different organs, especially the brain. The current study assessed the modulatory impact of Teucrium polium extract (TPE) on nicotine-induced behavioral and biochemical, alterations in mice brains. Methods: Twenty-four mice were divided into four groups and treated for three weeks. Group one was control, group two was subcutaneously injected with 2.5 mg/kg nicotine, group three received 100 mg/kg TPE orally, and group four was given 2.5 mg/kg of nicotine subcutaneously after an hour of oral administration of 100 mg/kg TPE. Result: The HPLC results of the plant extract showed the presence of 11 bioactive compounds. Nicotine administration increased anxiety and decreased locomotor activity and forelimb grip strength. Dopamine, serotonin, and acetylcholinesterase activity showed a significant decline in the nicotine-induced group. Treatment with TPE showed anxiolytic effects, modulated muscle strength and locomotor activity. Also, there was an increase in neurotransmitters compared with the nicotine group. In conclusion, TPE protected against nicotine-induced neurotoxicity through modulating behavior and neurotransmitter levels in mice. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Clinical Healthcare is the property of Chinese Journal of Clinical Healthcare and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Acupuncture & Tuina Science is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Functionalized multi‐walled carbon nanotubes (MWCNTs) have enticed remarkable attention in the field of electrochemical sensing applications. Dopamine (DA) is a monoamine neurotransmitter released in the brain acting as a chemical messenger that communicates messages between nerve cells and rest of the body. Therefore, there is a significant technological urge for the development of electrochemical sensors for DA in body fluids. In this context, nitrogen‐functionalized MWCNTs (TM‐CNT600) were fabricated by thermal annealing of carboxylic acid functionalized MWCNTs with thiourea at 600 °C under N2 atmosphere. The XPS spectrum reveals the presence of nitrogen‐containing functionalities in the as‐prepared TM‐CNT600. FTIR results show the presence of −OH, C−N and C−S functional groups. XPS further corroborates the FTIR results and quantifies the predominant functional groups in as‐prepared material. The material was investigated as a potential electrochemical sensor for the detection of dopamine (DA). In the case of TM‐CNT600/GCE, a linear relationship for DA concentration was observed in the range of 10.7–24.2 μM with the limit of detection (LOD) of 1.42 μM using linear sweep voltammetry (LSV). These results highlight the potential of TM‐CNT600 modified GCE as an efficient sensor for the electrochemical detection of DA in body fluids. [ABSTRACT FROM AUTHOR]

Tryptophan (Trp), tyrosine (Tyr), and histidine (His), known as three essential amino acids, are also precursors of vital neurotransmitters in brain nutrient metabolism. In this study, we have conducted a gas-phase study on their interactions with silver ions by a customized reflectron time-of-flight mass spectrometer combined with a magnetron sputtering source and a downstream flow tube reactor. It is unveiled that these physiological molecules are readily dissociated in the presence of Ag+ ions, giving rise to fragmentation and recombination products. Utilizing density functional theory calculations, we have clarified the reaction mechanism of the dissociative process. It is found that the silver ions facilitate the hydrogen atom transfer reaction followed by competitive Cα–Cβ and Cβ–Cγ bond dissociation. This study enriches the basic and precise properties of such neurotransmitter molecules and helps us understand similar physiological mechanisms in vivo. [ABSTRACT FROM AUTHOR]

Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific role in the brain. As a result, the existing body of literature on the subject is complex and sometimes conflicting. The primary objective of this review article is to provide a comprehensive overview of recent advancements in understanding the central nervous system role of CCK, with a specific emphasis on elucidating CCK's mechanisms for neuroplasticity, exploring its interactions with other neurotransmitters, and discussing its significant involvement in neurological disorders. Studies demonstrate that CCK mediates both inhibitory long‐term potentiation (iLTP) and excitatory long‐term potentiation (eLTP) in the brain. Activation of the GPR173 receptor could facilitate iLTP, while the Cholecystokinin B receptor (CCKBR) facilitates eLTP. CCK receptors' expression on different neurons regulates activity, neurotransmitter release, and plasticity, emphasizing CCK's role in modulating brain function. Furthermore, CCK plays a pivotal role in modulating emotional states, Alzheimer's disease, addiction, schizophrenia, and epileptic conditions. Targeting CCK cell types and circuits holds promise as a therapeutic strategy for alleviating these brain disorders. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of sour jujube kernel decoction combined with lily dihuang decoction plus minus combined with acupuncture on sleep quality and serum neurotransmitter levels in patients with yin deficiency insomnia after stroke.Methods: The selected cases were all from patients with insomnia after stroke admitted to our hospital during March 2018 to February2023, a total of 126 cases. According to the random number table method, the patients were divided into control group (conventional Western medicine treatment + acupuncture treatment, 63 cases) and observation group (63 cases received plus and minus treatment on the basis of sour jujube kernel soup and lily dihuang decoction, 63 cases) . The efficacy, TCM syndrome scores, and scale scores [Pittsburgh Sleep Quality Index Scale (PSQI), Sleep Status Self-rating Scale (SRSS) ], and serum neurotransmitters [serotonin (5-HT) and dopamine (DA) were compared between the two groups. Results: The total clinical effective rate of the observation group was higher than that of the control group, which showed statistical difference (P＜0.05) . After the treatment, the scores of the two groups were lower than those in the control group, which showed statistical difference (P＜0.05) . After treatment, PSQI score and SRSS score decreased in the two groups, and the observation group was lower than that in the control group, which showed statistical difference (P＜0.05) . After the treatment of the two groups, DA decreased and 5-HT increased, and the improvement in the observation group was greater than that in the control group, which showed statistical difference (P＜0.05) . Conclusion: The combination of sour jujube kernel decoction and lily dihuang decoction plus minus combined with acupuncture in the treatment of yin deficiency and fire type insomnia after stroke can effectively improve insomnia symptoms and regulate serum 5-HT and DA levels. [ABSTRACT FROM AUTHOR]

Background: Gastric motility disorder is an increasingly common problem among people with diabetes. Neurotransmitters have been recognized as critical regulators in the process of gastric motility. Previous study has shown that herb pair huanglian‐banxia (HL‐BX) can improve gastric motility, but the underlying mechanism is still unclear. The aim of this study was to further investigate the role of HL‐BX in modulating brain‐gut neurotransmission to promote gastric motility in diabetic rats, and to explore its possible mechanism. Methods: The diabetic rats were divided into five groups. Gastric emptying rate, intestinal propulsion rate, body weight, and average food intake were determined. Substance P (SP), 5‐ hydroxytryptamine (5‐HT), and glucagon‐like peptide −1 (GLP‐1) in the serum were measured by enzyme‐linked immunosorbent assay. Dopamine (DA) and norepinephrine (NE) in the brain were analyzed by high‐pressure liquid chromatography with a fluorescence detector. Protein expression of the tissues in the stomach and brain was determined by Western blot. Key Results: HL‐BX reduced average food intake significantly, increased body weight, and improved gastric emptying rate and intestinal propulsion rate. HL‐BX administration caused a significant increase in SP, GLP‐1, and 5‐HT, but a significant decrease in DA and NE. Interestingly, HL‐BX regulated simultaneously the different expressions of MAPK and its downstream p70S6K/S6 signaling pathway in the stomach and brain. Moreover, berberine exhibited a similar effect to HL‐BX. Conclusions: These results indicated that HL‐BX promoted gastric motility by regulating brain‐gut neurotransmitters through the MAPK signaling pathway. HL‐BX and MAPK provide a potential therapeutic option for the treatment of gastroparesis. [ABSTRACT FROM AUTHOR]

Existing methods for voxelwise transient dopamine (DA) release detection rely on explicit kinetic modeling of the [11C]raclopride PET time activity curve, which at the voxel level is typically confounded by noise, leading to poor performance for detection of low-amplitude DA release-induced signals. Here we present a novel data-driven, task-informed method—referred to as Residual Space Detection (RSD)—that transforms PET time activity curves to a residual space where DA release-induced perturbations can be isolated and processed. Using simulations, we demonstrate that this method significantly increases detection performance compared to existing kinetic model-based methods for low-magnitude DA release (simulated +100% peak increase in basal DA concentration). In addition, results from nine healthy controls injected with a single bolus of [11C]raclopride performing a finger tapping motor task are shown as proof-of-concept. The ability to detect relatively low magnitudes of dopamine release in the human brain using a single bolus injection, while achieving higher statistical power than previous methods, may additionally enable more complex analyses of neurotransmitter systems. Moreover, RSD is readily generalizable to multiple tasks performed during a single PET scan, further extending the capabilities of task-based single-bolus protocols. [ABSTRACT FROM AUTHOR]

Serotonin (5 hydroxytryptamine, 5-HT) is a biogenic amine of ancient origin that is widespread among animals. It plays multiple roles during development and in adults as neurotransmitter at synaptic level and neuro hormone controlling complex behaviors in both vertebrates and invertebrates. Tunicates occupy a key phylogenetic position to understand the evolution of serotonin functions since they are the sister group of vertebrates. The presence of serotonin in tunicates was first reported in adults of the ascidian Ciona robusta (formerly Ciona intestinalis) in the 1946. Since then, serotonin systems have been in many tunicate species and its functions during embryogenesis and metamorphosis explored. We reviewed the current knowledge about serotonin in these animals first by comparing its presence and localization in larvae and adults of different species. Then, we focused on the model organism Ciona for which data regarding sequences and expression patterns of genes involved in serotonin synthesis and function have been reported. Overall, we provided a comprehensive overview of serotonergic machinery in tunicates and gave hints for future studies in this field. [ABSTRACT FROM AUTHOR]

The autosomal recessive defect of aromatic L‐amino acid decarboxylase (AADC) leads to a severe neurological disorder with manifestation in infancy due to a pronounced, combined deficiency of dopamine, serotonin and catecholamines. The success of conventional drug treatment is very limited, especially in patients with a severe phenotype. The development of an intracerebral AAV2‐based gene delivery targeting the putamen or substantia nigra started more than 10 years ago. Recently, the putaminally‐delivered construct, Eladocagene exuparvovec has been approved by the European Medicines Agency and by the British Medicines and Healthcare products Regulatory Agency. This now available gene therapy provides for the first time also for AADC deficiency (AADCD) a causal therapy, leading this disorder into a new therapeutic era. By using a standardized Delphi approach members of the International Working Group on Neurotransmitter related Disorders (iNTD) developed structural requirements and recommendations for the preparation, management and follow‐up of AADC deficiency patients who undergo gene therapy. This statement underlines the necessity of a framework for a quality‐assured application of AADCD gene therapy including Eladocagene exuparvovec. Treatment requires prehospital, inpatient and posthospital care by a multidisciplinary team in a specialized and qualified therapy center. Due to lack of data on long‐term outcomes and the comparative efficacy of alternative stereotactic procedures and brain target sites, a structured follow‐up plan and systematic documentation of outcomes in a suitable, industry‐independent registry study are necessary. [ABSTRACT FROM AUTHOR]

Hyperactivity of granule cells in the ventral dentate gyrus (vDG) promotes vulnerability to chronic stress. However, which receptors in the vDG could be targeted to inhibit this hyperactivity and confer stress resilience is not known. The serotonin 1A receptor (5-HT 1A R) is a G i protein–coupled inhibitory receptor that has been implicated in stress adaptation, anxiety, depression, and antidepressant responses. 5-HT 1A Rs are highly expressed in the DG, but their potential to promote stress resilience by regulating granule cell activity has never been examined. We exposed male and female mice expressing 5-HT 1A Rs only in DG granule cells to 10 days of chronic social defeat stress (CSDS) and treated them with the 5-HT 1A R agonist 8-OH-DPAT every day 30 minutes before each defeat throughout the CSDS paradigm. We then used whole-cell current clamp recordings, immunohistochemistry for the immediate early gene cFos, corticosterone immunoassays, and behavioral testing to determine how activating 5-HT 1A Rs on granule cells affects DG activity, neuroendocrine stress responses, and avoidance behavior. We found that activating 5-HT 1A Rs hyperpolarized DG granule cells and reduced cFos+ granule cells in the vDG following CSDS, indicating that 5-HT 1A R activation rescued stress-induced vDG hyperactivity. Moreover, 5-HT 1A R activation dampened corticosterone responses to CSDS and prevented the development of stress-induced avoidance in the social interaction test and in the open field test. Our findings show that activating 5-HT 1A Rs on DG granule cells can prevent stress-induced neuronal hyperactivity of the vDG and confer resilience to chronic stress. [ABSTRACT FROM AUTHOR]