Search

Background and purposeTraumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes.Experimental approachAdult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation.Key resultsPost-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation.Conclusions and implicationsPost-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

Cranial irradiation used to control brain malignancies invariably leads to progressive and debilitating declines in cognition. Clinical efforts implementing hippocampal avoidance and NMDAR antagonism, have sought to minimize dose to radiosensitive neurogenic regions while normalizing excitatory/inhibitory (E/I) tone. Results of these trials have yielded only marginal benefits to cognition, prompting current studies to evaluate the potential of systemic extracellular vesicle (EV) therapy to restore neurocognitive functionality in the irradiated brain. Here we tested the hypothesis that EVs derived from inhibitory but not excitatory neuronal cultures would prove beneficial to cognition and associated pathology. Rats subjected to a clinically relevant, fractionated cranial irradiation paradigm were given multiple injections of either GABAergic- or glutamatergic-derived EV and subjected to behavioral testing. Rats treated with GABAergic but not glutamatergic EVs showed significant improvements on hippocampal- and cortical-dependent behavioral tasks. While each treatment enhanced levels of the neurotrophic factors BDNF and GDNF, only GABAergic EVs preserved granule cell neuron dendritic spine density. Additional studies conducted with GABAergic EVs, confirmed significant benefits on amygdala-dependent behavior and modest changes in synaptic plasticity as measured by long-term potentiation. These data point to a potentially more efficacious approach for resolving radiation-induced neurological deficits, possibly through a mechanism able to restore homeostatic E/I balance.

Cancer-related cognitive impairments (CRCI) are neurological complications associated with cancer treatment, and greatly affect cancer survivors' quality of life. Brain-derived neurotrophic factor (BDNF) plays an essential role in neurogenesis, learning and memory. The reduction of BDNF is associated with the decrease in cognitive function in various neurological disorders. Few pre-clinical studies have reported on the effects of chemotherapy and medical stress on BDNF levels and cognition. The present study aimed to compare the effects of medical stress and cisplatin on serum BDNF levels and cognitive function in 9-month-old female Sprague Dawley rats to age-matched controls. Serum BDNF levels were collected longitudinally during cisplatin treatment, and cognitive function was assessed by novel object recognition (NOR) 14 weeks post-cisplatin initiation. Terminal BDNF levels were collected 24 weeks after cisplatin initiation. In cultured hippocampal neurons, we screened three neuroprotective agents, riluzole (an approved treatment for amyotrophic lateral sclerosis), as well as the ampakines CX546 and CX1739. We assessed dendritic arborization by Sholl analysis and dendritic spine density by quantifying postsynaptic density-95 (PSD-95) puncta. Cisplatin and exposure to medical stress reduced serum BDNF levels and impaired object discrimination in NOR compared to age-matched controls. Pharmacological BDNF augmentation protected neurons against cisplatin-induced reductions in dendritic branching and PSD-95. Ampakines (CX546 and CX1739) and riluzole did not affect the antitumor efficacy of cisplatin in vitro. In conclusion, we established the first middle-aged rat model of cisplatin-induced CRCI, assessing the contribution of medical stress and longitudinal changes in BDNF levels on cognitive function, although future studies are warranted to assess the efficacy of BDNF enhancement in vivo on synaptic plasticity. Collectively, our results indicate that cancer treatment exerts long-lasting changes in BDNF levels, and support BDNF enhancement as a potential preventative approach to target CRCI with therapeutics that are FDA approved and/or in clinical study for other indications.

Purpose: Compare tracking groups with cognitive control functions and plasma brain-derived neurotrophic factors concentrations from childhood to adolescence. Methods: This is a prospective study with 3 years of follow-up. At baseline, data from 394 individuals were collected (11.7 y), and data were obtained from 134 adolescents (14.9 y) at the 3-year follow-up. At both time points, anthropometric and maximal oxygen uptake data were collected. Cardiorespiratory fitness (CRF) groups were classified into high or low CRF. At follow-up, cognitive outcomes were collected via the Stroop and Corsi block test; plasma brain-derived neurotrophic factors concentrations were also analyzed. Results: Comparisons demonstrated that maintaining high CRF over 3 years results in shorter reaction time, better inhibitory control, and higher working memory values. Likewise, the group that moved from low to high CRF over 3 years presented better reaction time. Plasma brain-derived neurotrophic factors concentrations were higher for the group that increased its CRF over the 3 years in relation to the low–low group (90.58 pg·mL−1; P =.004). However, after scaling by an allometric approach, differences were only found for reaction time and working memory between high–high and high–low groups. Conclusion: Maintaining high CRF over 3 years was positively related to reaction time and working memory in relation to adolescents that decreased their levels of CRF. [ABSTRACT FROM AUTHOR]

In this work, photophysical properties of the flavone-based dyes APG, BCN, CYS, LUT, and OX-A were investigated using TD-DFT calculations at PBE0/6-311++G (d,p) level in the gas phase and solvent media. The structural parameters, absorption and emission spectra, potential energy curves, natural charges, electron density properties, reduced density gradient, and protein–ligand docking properties were calculated. In the S1 state, the normal form of all dyes was directly converted to its tautomeric T form by no energy barrier. The results demonstrated that O1–H2···O6 H-bonding at S0 state is stronger than O1···H2–O6 one at S1 state. Upon photoexcitation to the S1 state, the flavones exhibit keto fluorescence emission in the near-infrared (NIR) wavelengths of 848.0 nm for APG to 1143.1 nm for OX-A, making the application of these molecules more attractive in the medical and physiological diagnostics. In addition, the anti-aging properties of the flavonoids were studied by docking process on the two aging targets brain-derived neurotrophic factor (BDNF) and nerve growth factors (NGF). Our study can provide insights into the design of a flavone-based ESIPT fluorescent probe and its anti-aging properties which might inspire future applications in the field of chemical sensing, imaging and drug design. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is crucial for neuronal survival and may be implicated in the pathophysiological process of depression. This study aimed to prospectively investigate the association between serum BDNF and post-stroke depression (PSD) at 3 months in a multicenter cohort study. A total of 611 ischemic stroke patients with serum BDNF measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24-item Hamilton Depression Rating Scale to assess depression status at 3 months after ischemic stroke, and PSD was defined as a score of ≥8. Baseline serum BDNF was inversely associated with the risk of depression after ischemic stroke. The multivariable-adjusted odds ratio of PSD for the highest tertile of BDNF was 0.53 (95 % confidence interval, 0.34–0.82; P for trend = 0.004) compared with the lowest tertile. Multivariable-adjusted spline regression model also showed a linear does-response association between serum BDNF levels and PSD at 3 months (P for linearity = 0.006). In addition, adding serum BDNF to conventional risk factors significantly improved the risk reclassification of PSD (net reclassification improvement: 16.98 %, P = 0.039; integrated discrimination index: 0.93 %, P = 0.026). All patients in this study were Chinese, so our findings should be applied to other populations cautiously. Higher serum BDNF levels at baseline were significantly associated with a decreased risk of PSD at 3 months, suggesting that BDNF might be a valuable predictive biomarker and potential therapeutic target for PSD among ischemic stroke patients. • High serum BDNF levels were associated with a decreased risk of 3-month PSD. • There was an inverse linear dose-response association between BDNF and 3-month PSD. • Adding BDNF to conventional risk factors improved the risk reclassification for PSD. [ABSTRACT FROM AUTHOR]

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects various regions of the brain. Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive method utilized for stimulating different brain areas. Our objective is to alleviate ASD symptoms using high-frequency rTMS (HF-rTMS) in a rat model of ASD induced by valproic acid (VPA). Methods: In this investigation, we applied HF-rTMS for ASD treatment, focusing on the hippocampus. Behavioral assessments encompassed core ASD behaviors, as well as memory and recognition tests, alongside evaluations of anxiety and stress coping strategies. Additionally, we analyzed oxidative stress and a related inflammation marker, as well as other biochemical components. We assessed brain-derived neurotrophic factor (BDNF), Microtubule-associated protein-2 (MAP-2), and synaptophysin (SYN). Finally, we examined dendritic spine density in the CA1 area of the hippocampus. Results: The results demonstrated that HF-rTMS successfully mitigated ASD symptoms, reducing oxidative stress and improving various biochemical factors, along with an increase in dendritic spine density. Discussion: Collectively, our data suggests that HF-rTMS may effectively alleviate ASD symptoms. These findings could be valuable in clinical research and contribute to a better understanding of the mechanisms underlying ASD. [ABSTRACT FROM AUTHOR]

Grapheme-color synesthesia is a normal and healthy variation of human perception. It is characterized by the association of letters or numbers with color perceptions. The etiology of synesthesia is not yet fully understood. Theories include hyperconnectivity in the brain, cross-activation of adjacent or functionally proximate sensory areas of the brain, or various models of lack of inhibitory function in the brain. The growth factor brain-derived neurotrophic (BDNF) plays an important role in the development of neurons, neuronal pathways, and synapses, as well as in the protection of existing neurons in both the central and peripheral nervous systems. ELISA methods were used to compare BDNF serum concentrations between healthy test subjects with and without grapheme-color synesthesia to establish a connection between concentration and the occurrence of synesthesia. The results showed that grapheme-color synesthetes had an increased BDNF serum level compared to the matched control group. Increased levels of BDNF can enhance the brain's ability to adapt to changing environmental conditions, injuries, or experiences, resulting in positive effects. It is discussed whether the integration of sensory information is associated with or results from increased neuroplasticity. The parallels between neurodegeneration and brain regeneration lead to the conclusion that synesthesia, in the sense of an advanced state of consciousness, is in some cases a more differentiated development of the brain rather than a relic of early childhood. [ABSTRACT FROM AUTHOR]

Objective To investigate the predictive value of National Institutes of Health Stroke Scale (NIHSS) score, serum brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) in post-stroke depression (PSD). Methods A total of 180 patients with stroke were selected and divided into the PSD group (n=80, HAMD≥8 points) and the non-PSD (NPSD) group (n=100, HAMD＜8 points), according to HAMD score at 3 months after stroke. The basic information, NIHSS score, serum BDNF and IL-6 were compared between the two groups. The influencing factors of PSD were analyzed by Logistic regression method. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of NIHSS score, serum BDNF and IL-6 for PSD. Results Compared with the NPSD grope, low density lipoprotein cholesterol (LDL-C) and serum BDNF level were significantly lower, NIHSS score and serum IL-6 level were significantly increased in the PSD group (P＜0.05). Results of Logistic regression analysis showed that increased NIHSS score and serum IL-6 were risk factors for PSD, and increased serum BDNF was the protective factor in patents with PSD (P＜0.05). The area under curve (AUC) of NIHSS score, serum BDNF and IL-6 and their combination prediction of PSD were 0.762, 0.746, 0.796 and 0.839, respectively. The sensitivity of the combined prediction was 86.0% and a specificity was 95.0%. Conclusion Compared with NPSD patients, the NIHSS score and serum IL-6 level are increased, and the serum BDNF level is decreased in patients with PSD. The combination of all three has a high predictive value for patients of PSD. [ABSTRACT FROM AUTHOR]

Purpose: Short-term intake of the egg-protein hydrolysate Newtricious (NWT)-03 improved executive function, but underlying mechanisms and long-term effects, including other cognitive domains, are unknown. Methods: A 36-week randomized controlled trial involving 44 overweight/obese individuals experiencing elevated Subjective Cognitive Failures (SCF; aged 60–75 years) assessed the impact of daily consumption of 5.7 g of NWT-03 or placebo powders on cognitive performance (psychomotor speed, executive function, memory) and Cerebral Blood Flow (CBF), a marker of brain vascular function. Cognitive performance was evaluated using a neurophysiological test battery (CANTAB) and CBF was measured using magnetic resonance imaging perfusion method Arterial Spin Labeling (ASL). Serum samples were collected to determine brain-derived neurotrophic factor (BDNF) concentrations. Results: Anthropometrics, and energy and nutrient intakes remained stable throughout the trial. NWT-03 was well tolerated, and compliance was excellent (median: 99%; range: 87–103%). No overall intervention effects were observed on cognitive performance or CBF, but post-hoc analyses revealed significant improvements on executive function in women, but not men. Specifically, a reduction of 74 ms in reaction latency on the multitasking task (95% CI: −134 to −15; p = 0.02), a reduction of 9 between errors (95%CI: −14 to −3; p < 0.001), and a reduction of 9 total errors (95%CI: −15 to −3; p < 0.001) on the spatial working memory task were found in women. No intervention effects were observed on serum BDNF concentrations (p = 0.31). Conclusion: Long-term consumption of NWT-03 improved multitasking abilities and working memory in women with elevated SCF. Brain vascular function remained unaffected. Sex differences in executive function require additional clarification. [ABSTRACT FROM AUTHOR]

Objective: Melissa officinalis (MO) hydroalcoholic extract has shown neuroprotective effects. We assess the possible therapeutic effects of Melissa officinalis extract (MOE) on blood biochemical and Brain-Derived Neurotrophic Factor (BDNF) levels as well as neurobehavioral consequences of high-fat-diet (HFD)-induced obese rats. Materials and Methods: Eighty male Wistar rats weighing between 180 and 220 g were divided into two groups at the beginning of the experiment and fed with normal diet (ND) or HFD for 5 weeks. Then, each group was divided into four subgroups (10 rats in each group) and treated daily with MOE (50, 100, 150 mg/kg, intraperitoneal) or vehicle for another two weeks. At the end of the experiments, fasting blood glucose (FBG), blood lipid profile, and serum brain-derived neurotrophic factor (BDNF) levels were measured. The sucrose preference test (anhedonia and depression), open field test (locomotor), elevated plus maze (anxiety), Y-maze (working memory), and Morris water maze test (spatial memory) were done. Results: Feeding with HFD for 7 weeks caused obesity, anhedonia, anxiety, depression and learning and memory disorders in rats and a decrease in serum BDNF level. Administration of MOE at 100 or 150 mg/kg to HFD-fed rats decreased weight gain, FBG, and serum levels of total low-density lipoprotein cholesterol and increased serum BDNF levels. It also improved changes in locomotor activity, anxiety, depression, and learning and memory in HFD-fed rats. Conclusion: The results show that MOE has a therapeutic effect on model rats with HFD-induced metabolic and neurobehavioral abnormalities through regulation of BDNF secretion. [ABSTRACT FROM AUTHOR]

Introduction: Human neuroblastoma cell line SH-SY5Y is a frequently used experimental cellular model in a variety of neuropsychiatric and neurodegenerative disorders. It is crucial to use a culture protocol that supports the fully differentiation of SH-SY5Y into neuron-like phenotype for the consistency of the results with neurons in vivo. However, a standardized neuronal differentiation protocol for SHSY5Y cells still does not exist. Numerous differentiation methods have been proposed in the literature, yet SH-SY5Y cells with stronger neuronal characteristics and a more favorable environment for these differentiated cells are required in order to best representation of neurons. Therefore, in the study, we aimed to establish a more successful differentiation protocol for SH-SY5Y cells based on the primary neuron culture technique, which neuronal maturation is very well defined. Methods: In the study, we rearranged previous SH-SY5Y differentiation protocols, combined them with our primary neuron culture protocol and created a robust and reproducible protocol for differentiation of SH-SY5Y. Results: Our proposed "retinoic acid+brain-derived neurotrophic factor (RA+BDNF)-induced 7 days differentiation (conalbumin- on day 4) protocol provided well developed neurites, adequate expression and localization of neuronal and synaptic markers resembling mature neurons. Conclusion: The differentiation protocol we present can enable researchers to obtain satisfactory and properly differentiated SH-SY5Y cells in each independent experiment, achieving the closest possible in vivo results. [ABSTRACT FROM AUTHOR]

Background: Premature ejaculation (PE) is the most prevalent sexual dysfunction among men. Eejaculation involves a complex nervous mechanism in which the ejaculatory centers play a key role in modulating sperm emission. Although treatment possibilities span from psychotherapy to pharmacological approaches, results show inconsistent efficacy. In this context, the emergence of repetitive transcranial magnetic stimulation (rTMS) as a non‐invasive neuromodulatory approach represents a compelling avenue for potential therapeutic exploration. Objective: To investigate whether high‐frequency transcranial magnetic stimulation can modulate the ejaculatory behavior of rats with rapid ejaculation by altering neurotransmitter levels and neuroplasticity in the hippocampus. Methods: Rats have been screened for rapid ejaculation by observing behavioral indices of mating, and subsequently divided into two groups. The intervention group was administered with a 10 Hz rTMS stimulation, whereas the control group received a sham procedure. Upon the delivery of rTMS, we investigated ejaculation latency (EL), the hippocampal 5‐hydroxytryptamine (5‐HT) concentration, brain‐derived neurotrophic factor (BDNF), synaptophysin (SYN), and postsynaptic density protein 95 (PSD95) expressions, as well as BDNF‐receptor tyrosine kinase receptor B (TrkB) pathway upregulation. Results: After 14 days, EL was increased in the intervention group compared with the control group. 5‐HT concentration in the hippocampal region was increased, and high‐frequency rTMS activated the BDNF and TrkB pathways, including phosphorylation of cAMP response element‐binding protein (CREB), and upregulated the transcription and protein expression of SYN, and PSD95. Conclusion: RTMS upregulates BDNF, SYN, and PSD95 expression through activation of the BDNF–TrkB pathway and increases brain 5‐hydroxytryptamine thereby regulating neuroplasticity and improving ejaculation. [ABSTRACT FROM AUTHOR]

Sulforaphane is a natural compound with neuroprotective activity, but its effects on hypothalamus remain unknown. In line with this, astrocytes are critical cells to maintain brain homeostasis, and hypothalamic astrocytes are fundamental for sensing and responding to environmental changes involved in a variety of homeostatic functions. Changes in brain functionality, particularly associated with hypothalamic astrocytes, can contribute to age-related neurochemical alterations and, consequently, neurodegenerative diseases. Thus, here, we investigated the glioprotective effects of sulforaphane on hypothalamic astrocyte cultures and hypothalamic cell suspension obtained from aged Wistar rats (24 months old). Sulforaphane showed anti-inflammatory and antioxidant properties, as well as modulated the mRNA expression of astroglial markers, such as aldehyde dehydrogenase 1 family member L1, aquaporin 4, and vascular endothelial growth factor. In addition, it increased the expression and extracellular levels of trophic factors, such as glia-derived neurotrophic factor and nerve growth factor, as well as the release of brain-derived neurotrophic factor and the mRNA of TrkA, which is a receptor associated with trophic factors. Sulforaphane also modulated the expression of classical pathways associated with glioprotection, including nuclear factor erythroid-derived 2-like 2, heme oxygenase-1, nuclear factor kappa B p65 subunit, and AMP-activated protein kinase. Finally, a cell suspension with neurons and glial cells was used to confirm the predominant effect of sulforaphane in glial cells. In summary, this study indicated the anti-aging and glioprotective activities of sulforaphane in aged astrocytes. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is vital for synaptic plasticity, cell persistence, and neuronal development in peripheral and central nervous systems (CNS). Numerous intracellular signalling pathways involving BDNF are well recognized to affect neurogenesis, synaptic function, cell viability, and cognitive function, which in turn affects pathological and physiological aspects of neurons. Stroke has a significant psycho-socioeconomic impact globally. Central post-stroke pain (CPSP), also known as a type of chronic neuropathic pain, is caused by injury to the CNS following a stroke, specifically damage to the somatosensory system. BDNF regulates a broad range of functions directly or via its biologically active isoforms, regulating multiple signalling pathways through interactions with different types of receptors. BDNF has been shown to play a major role in facilitating neuroplasticity during post-stroke recovery and a pro-nociceptive role in pain development in the nervous system. BDNF-tyrosine kinase receptors B (TrkB) pathway promotes neurite outgrowth, neurogenesis, and the prevention of apoptosis, which helps in stroke recovery. Meanwhile, BDNF overexpression plays a role in CPSP via the activation of purinergic receptors P2X4R and P2X7R. The neuronal hyperexcitability that causes CPSP is linked with BDNF-TrkB interactions, changes in ion channels and inflammatory reactions. This review provides an overview of BDNF synthesis, interactions with certain receptors, and potential functions in regulating signalling pathways associated with stroke and CPSP. The pathophysiological mechanisms underlying CPSP, the role of BDNF in CPSP, and the challenges and current treatment strategies targeting BDNF are also discussed. [ABSTRACT FROM AUTHOR]

As the aging population continues to increase, aging-related inflammation, oxidative stress, and neurodegenerative diseases have become serious global health threats. Resveratrol, a star molecule in natural polyphenols, has been widely reported to have physiological activities such as anti-aging, anti-inflammatory, antioxidant, and neuroprotection. However, its poor water solubility, rapid metabolism, low bioavailability and poor targeting ability, which limits its application. Accordingly, a brain-targeted resveratrol liposome (ANG-RES-LIP) was developed to solve these issues. Experimental results showed that ANG-RES-LIP has a uniform size distribution, good biocompatibility, and a drug encapsulation rate of over 90%. Furthermore, in vitro cell experiments showed that the modification of the targeting ligand ANG significantly increased the capability of RES to cross the BBB and neuronal uptake. Compared with free RES, ANG-RES-LIP demonstrated stronger antioxidant activity and the ability to rescue oxidatively damaged cells from apoptosis. Additionally, ANG-RES-LIP showed the ability to repair damaged neuronal mitochondrial membrane potential. In vivo experiments further demonstrated that ANG-RES-LIP improved cognitive function by reducing oxidative stress and inflammation levels in the brains of aging model mice, repairing damaged neurons and glial cells, and increasing brain-derived neurotrophic factor. In summary, this study not only provides a new method for further development and application of resveratrol but also a promising strategy for preventing and treating age-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models. [ABSTRACT FROM AUTHOR]

Objective(s): Prenatal stress (PS) can adversely affect cognitive and psychological functions in the offspring. This study aimed to determine the effect of PS and extremely low-frequency electromagnetic field (ELF-EMF) on spatial memory, serum corticosterone, brain-derived neurotrophic factor (BDNF) concentrations, and hippocampal BDNF levels in adult male offspring. Materials and Methods: Female Wistar rats were randomly divided into four groups (n=6): Control, Stress, ELF-EMF (exposure to ELF-EMF), and S+EMF (simultaneous exposure to stress and the ELFEMF) groups. Animals received interventions for 21 days before and 21 days during pregnancy (a total of 42 days). On the offspring’s 90th postnatal day (PND), spatial memory was tested using Morris Water Maze, serum Corticosterone and BDNF levels were measured by the ELISA method, and hippocampal BDNF levels were measured by Western blotting. Results: PS did not affect spatial memory in the adult male offspring; however, it significantly (P<0.05) increased se-rum corticosterone levels compared to the control and EMF groups. Simultaneous induction of stress with ELF-EMF disrupted the memory acquisition phase. Serum and hippocampal BDNF levels increased significantly (P<0.05) in the EMF group compared to the stress group. Conclusion: Based on our findings, PS can increase serum corticosterone levels without affecting spatial memory. However, induction of ELF-EMF with stress has a destructive effect on spatial memory with no change in the corticosterone levels. Compared to stress, prenatal exposure to ELF-EMF increases serum and hippocampal BDNF levels. Further studies are needed to determine the underlying mechanisms of these findings. [ABSTRACT FROM AUTHOR]

Objective Allelic variation in the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been shown to moderate rates of cognitive decline in preclinical sporadic Alzheimer's disease (AD; i.e. Aβ + older adults), and pre-symptomatic autosomal dominant Alzheimer's disease (ADAD). In ADAD, Met66 was also associated with greater increases in CSF levels of total-tau (t-tau) and phosphorylated tau (p-tau181). This study sought to determine the extent to which BDNF Val66Met is associated with changes in episodic memory and CSF t-tau and p-tau181 in Aβ + older adults in early-stage sporadic AD. Method Aβ + Met66 carriers (n  = 94) and Val66 homozygotes (n  = 192) enrolled in the Alzheimer's Disease Neuroimaging Initiative who did not meet criteria for AD dementia, and with at least one follow-up neuropsychological and CSF assessment, were included. A series of linear mixed models were conducted to investigate changes in each outcome over an average of 2.8 years, covarying for CSF Aβ42, APOE ε4 status, sex, age, baseline diagnosis, and years of education. Results Aβ + Met66 carriers demonstrated significantly faster memory decline (d  = 0.33) and significantly greater increases in CSF t-tau (d  = 0.30) and p-tau181 (d  = 0.29) compared to Val66 homozygotes, despite showing equivalent changes in CSF Aβ42. Conclusions These findings suggest that reduced neurotrophic support, which is associated with Met66 carriage, may increase vulnerability to Aβ-related tau hyperphosphorylation, neuronal dysfunction, and cognitive decline even prior to the emergence of dementia. Additionally, these findings highlight the need for neuropsychological and clinicopathological models of AD to account for neurotrophic factors and the genes which moderate their expression. [ABSTRACT FROM AUTHOR]

Depression and chronic pain frequent co-occur, exacerbating each other's symptoms and hindering treatment. Emerging studies have highlighted abnormal gut microbiota in both conditions. Previous studies have demonstrated the clinical effectiveness of electro-acupuncture (EA) in managing these conditions, yet the underlying mechanisms remain elusive. Spared nerve injury (SNI) was employed to induce chronic pain and depression-like behavior. Rats were randomly assigned to sham SNI (SS), SNI, and EA groups. SNI surgery was performed on all rats, except those in SS group, which underwent sham SNI surgery. Then EA group received 5 weeks of EA treatment. Pain and depression-like behavior were assessed through paw withdrawal threshold, sucrose-preference test, and forced swim test. Gut microbiota composition was analyzed via 16S rDNA sequencing. Brain-Derived Neurotrophic Factor (BDNF) and acetylation-related proteins in the medial prefrontal cortex (mPFC) were evaluated through enzyme-linked immunosorbent assay and western blot. EA treatment significantly ameliorated pain and depression-like behavior. The 16S rDNA sequencing showed EA modulated gut microbiota composition, increased short-chain fatty acids (SCFAs)-producing bacteria, including Akkermansi, Ruminococcaceae and Lachnospiraceae family, particularly Akkermansia. Furthermore, EA increased BDNF, AcH3 and decreased HDAC2 in mPFC. Notably, SCFAs-producing bacteria exhibited a negative correlation with HDAC2 levels. This study exclusively investigated microbiota differences resulting from EA stimulation, without delving into the functional variations brought about by these microbial distinctions. The therapeutic effects of EA on the comorbidity of chronic pain and depression may involve the modulation of the gut microbiota, resulting in histone acetylation changes and upregulation of BDNF. • EA ameliorated pain and depression-like behaviors in SNI rats. • EA modulated the gut microbiota, increased the abundance of SCFAs-producing bacteria, particularly Akkermansia- muciniphila. • EA inhibited histone deacetylase in SNI rats. [ABSTRACT FROM AUTHOR]

Rationale: Clinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear. Objectives: This study was to observe the antidepressant effect and expression of BDNF and β-catenin in IL by allopregnanolone (ALLO) treatment or the selective activation or inhibition of IL neurons using a chemogenetic approach in a pseudopregnancy model of PPD. Methods: Administration of estradiol combined with progesterone and the abrupt withdrawal of estradiol simulated the pregnancy and early postpartum periods to induce depression in ovariectomized rats. The relative expression levels of β-catenin and BDNF were observed by western blotting. Results: Immobility time was significantly increased in the forced swim test and open-arm movement was reduced in the elevated plus maze test in the estradiol-withdrawn rats. After ALLO treatment, the immobility time were lower and open-arm traveling times higher than those of the estradiol-withdrawn rats. Meanwhile, the expression level of BDNF or β-catenin in the IL was reduced significantly in estradiol-withdrawn rats, which was prevented by treatment with ALLO. The hM3Dq chemogenetic activation of pyramidal neurons in the IL reversed the immobility and open-arm travel time trends in the estradiol-withdrawal rat model, but chemogenetic inhibition of IL neurons failed to affect this. Upregulated BDNF and β-catenin expression and increased c-Fos in the basolateral amygdala were found following IL neuron excitation in model rats. Conclusions: Our results demonstrated that pseudopregnancy and estradiol withdrawal produced depressive-like behavior and anxiety. ALLO treatment or specific excitement of IL pyramidal neurons relieved abnormal behaviors and upregulated BDNF and β-catenin expression in the IL in the PPD model, suggesting that hypofunction of IL neurons may be involved in the pathogenesis of PPD. [ABSTRACT FROM AUTHOR]

Diabetic encephalopathy (DE) is a severe complication of the central nervous system associated with diabetes. In this study, we investigated the regulatory role of mammalian target of rapamycin (mTOR) on nuclear factor κB (NF-κB) in mice with DE, and the neuroprotective effect and therapeutic mechanisms of luteolin, a natural flavonoid compound with anti-inflammatory, antioxidant, and neuroprotective properties. The results indicated that treatment with luteolin improved the degree of cognitive impairment in mice with DE. It also decreased the levels of phosphorylated mTOR, phosphorylated NF-κB, and histone deacetylase 2 (HDAC2) and increased the expression of brain-derived neurotrophic factor and synaptic-related proteins. Furthermore, protein-protein interaction and the Gene Ontology analysis revealed that luteolin was involved in the regulatory network of HDAC2 expression through the mTOR/NF-κB signaling cascade. Our bioinformatics and molecular docking results indicated that luteolin may also directly target HDAC2, as an HDAC2 inhibitor, to alleviate DE, complementing mTOR/NF-κB signaling inhibition. Analysis of luteolin's target proteins and their interactions suggest an effect on HDAC2 and cognition. In conclusion, HDAC2 and tau hyperphosphorylation are regulated by the mTOR/NF-κB signaling cascade in DE, and luteolin is found to reverse these effects, demonstrating its protective role in DE. Article Highlights: Luteolin's neuroprotective effect on diabetic encephalopathy (DE) targets mTOR/NF-κB signaling. Decreases in phosphorylated mTOR, phosphorylated NF-κB, and HDAC2, and increases in brain-derived neurotrophic factor and synaptic proteins were demonstrated. Luteolin's potential direct targeting to HDAC2 is highlighted, providing a new approach for DE treatment. [ABSTRACT FROM AUTHOR]

Objective: Ischemic stroke is the leading cause of mortality and disability worldwide with more than half of survivors living with serious neurological sequelae thus, it has recently attracted considerable attention in the field of medical research. Neurogenesis is the process of formation of new neurons in the brain, including the human brain, from neural stem/progenitor cells [NS/PCs] which reside in neurogenic niches that contain the necessary substances for NS/PC proliferation, differentiation, migration, and maturation into functioning neurons which can integrate into a pre-existing neural network. Neurogenesis can be modulated by many exogenous and endogenous factors, pathological conditions. Both brain-derived neurotrophic factor, and flavonoids can modulate the neurogenic process in physiological conditions and after various pathological conditions including ischemic insults. Aim: This review aims to discuss neurogenesis after ischemic insults and to determine the role of flavonoids and BDNF on neurogenesis under physiological and pathological conditions with a concentration on ischemic insults to the brain in particular. Method: Relevant articles assessing the impact of flavonoids and BDNF on neurogenic processes in various physiological/pathological conditions including ischemic insults within the timeline of 1965 until 2023 were searched using the PubMed database. Conclusions: The selected studies have shown that ischemic insults to the brain induce NS/PC proliferation, differentiation, migration, and maturation into functioning neurons integrating into a pre-existing neural network. Flavonoids and BDNF can modulate neurogenesis in the brain in various physiological/pathological conditions including ischemic insults. In conclusion, flavonoids and BDNF may be involved in post-ischemic brain repair processes through enhancing endogenous neurogenesis. [ABSTRACT FROM AUTHOR]

This article explores the role of neurolipids in the treatment of dementia, specifically Alzheimer's disease, Parkinson's disease, and Huntington's disease. The authors discuss the involvement of various neurolipidic systems, such as the endocannabinoid, lysophosphatidic acid, and sphingosine 1-phosphate systems, in these neurodegenerative diseases. They present recent findings from experiments and clinical trials that suggest the potential therapeutic benefits of targeting these systems. However, the authors also acknowledge the need for further research in this field. Overall, the article suggests that targeting neurolipid systems could be a promising approach for developing innovative therapies for dementia. [Extracted from the article]

Background: Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise's influence on adult diabetic rats' memory and neuroplasticity. Methods: Male Wistar pups were divided into Control, Diabetes, Exercise Training, and Diabetes exercise groups. Diabetes was induced on day 23 with Alloxan (200 mg/kg). A 3-week regimen included aerobic and resistance training thrice weekly. The aerobic intensity was 70%, and resistance varied from 50% to 100% of the maximal carrying capacity (MCC). Following the last training sessions, spatial memory and retrieval tests were performed in infancy, childhood, and emerging adulthood using the Morris Water Maze test (MWM). The hippocampus was excised to measure protein and gene expression of brain-derived neurotrophic factor (BDNF), calmodulin-dependent protein kinase (CAMKII), N-methyl-D-aspartate receptors (NMDAR), and cAMP-response element-binding protein (CREB) by western blotting and reverse transcription–polymerase-chain reaction (RT-PCR) methods. Blood samples were collected during each developmental stage to measure glucose levels, at the study's conclusion, to assess Interleukin-1β levels using the ELISA method. The Nissel staining assessed dead hippocampal cells in CA1. Results: Post-natal exercise improved spatial memory (p < 0.05) and glucose levels (p < 0.05) in diabetic rats during adolescence and emerging adulthood. Despite reduced mRNA expression (NMDAR 40%, BDNF 62%, CREB 43%, CAMKII 66%), diabetic rats, by study end, showed increased BDNF, NMDARR, CAMKII, CREB protein/gene expression (p < 0.05) in emerging adulthood for both training groups. Conclusion: Early-life exercise influenced hippocampal BDNF/NMDAR-CAMKII/CREB pathways in a diabetic rat model, highlighting post-natal exercise's role in neuroplasticity memory enhancement and improved glucose level. [ABSTRACT FROM AUTHOR]

The regeneration of peripheral nerves after injury is often slow and impaired, which may be associated with weakened and denervated muscles subsequently leading to atrophy. Adipose-derived stem cells (ADSCs) are often regarded as cell-based therapeutic candidate due to their regenerative potential. The study aims to assess the therapeutic efficacy of gene-modified ADSCs on sciatic nerve injury. We lentivirally transduced ADSCs with shRNA-TWIST1 and transplanted modified cells to rats undergoing sciatic nerve transection and repair. Results showed that TWIST1 knockdown accelerated functional recovery of rats with sciatic nerve injury as faster nerve conduction velocity and higher wire hang scores obtained by rats transplanted with TWIST1-silenced ADSCs than scramble ADSCs. Although the rats experienced degenerated axons and decreased myelin sheath thickness after sciatic nerve injury 8 weeks after operation, those transplanted with TWIST1-silenced ADSCs exhibited more signs of regenerated nerve fibers surrounded by newly formed myelin sheaths than those with scramble ADSCs. The rats transplanted with TWIST1-silenced ADSCs presented increased expressions of neurotrophic factors including neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) in the sciatic nerves than those with scramble ADSCs. These results suggest that genetically modifying TWIST1 in ADSCs could facilitate peripheral nerve repair after injury in a more efficient way than that with ADSCs alone. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Biomarker responses to intensive decompression indicate systemic proinflammatory responses and possible neurological stress. To further investigate responses, 12 additional brain and lung biomarkers were assayed. METHODS: A total of 15 healthy men (20 to 50 yr) undertook consecutive same-day ascents to 25,000 ft (7620 m), following denitrogenation, breathing 100% oxygen. Venous blood was sampled at baseline (T0), after the second ascent (T8), and next morning (T24). Soluble protein markers of brain and lung insult were analyzed by enzyme-linked immunosorbent assay with plasma microparticles quantified using flow cytometry. RESULTS: Levels of monocyte chemoattractant protein-1 and high mobility group box protein 1 were elevated at T8, by 36% and 16%, respectively, before returning to baseline. Levels of soluble receptor for advanced glycation end products fell by 8%, recovering by T24. Brain-derived neurotrophic factor rose by 80% over baseline at T24. Monocyte microparticle levels rose by factors of 3.7 at T8 and 2.7 at T24 due to early and late responses in different subjects. Other biomarkers were unaffected or not detected consistently. DISCUSSION: The elevated biomarkers at T8 suggest a neuroinflammatory response, with later elevation of brain-derived neurotrophic factor at T24 indicating an ongoing neurotrophic response and incomplete recovery. A substantial increase at T8 in the ratio of high mobility group box protein 1 to soluble receptor for advanced glycation end products suggests this axis may mediate the systemic inflammatory response to decompression. The mechanism of neuroinflammation is unclear but elevation of monocyte microparticles and monocyte chemoattractant protein-1 imply a key role for activated monocytes and/or macrophages. [ABSTRACT FROM AUTHOR]

• Dapagliflozin enhances the Nrf2 pathway and increases IGF-1, IGFBP-3, and BDNF levels in a rat ASD model. • Treatment reduces TNF-α, IL-17, and MDA levels, demonstrating anti-inflammatory properties. • Dapagliflozin improves cognitive and memory functions in PPA-induced ASD. • Modulates apoptotic mechanisms, suggesting therapeutic potential for oxidative stress and inflammation-related ASD. • Further studies needed to explore additional pathways and validate clinical potential. The biological effects of dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reveal its antioxidant and anti-inflammatory properties, suggesting therapeutic benefits beyond glycemic control. This study explores the neuroprotective effects of dapagliflozin in a rat model of autism spectrum disorder (ASD) induced by propionic acid (PPA), characterized by social interaction deficits, communication challenges, repetitive behaviors, cognitive impairments, and oxidative stress. Our research aims to find effective treatments for ASD, a condition with limited therapeutic options and significant impacts on individuals and families. PPA induces ASD-like symptoms in rodents, mimicking biochemical and behavioral features of human ASD. This study explores dapagliflozin's potential to mitigate these symptoms, providing insights into novel therapeutic avenues. The findings demonstrate that dapagliflozin enhances the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway and increases levels of neurotrophic and growth factors such as brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein-3 (IGFBP-3). Additionally, dapagliflozin reduces pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17), and decreases the oxidative stress marker malondialdehyde (MDA). Dapagliflozin's antioxidant properties support cognitive functions by modulating apoptotic mechanisms and enhancing antioxidant capacity. These combined effects contribute to reducing learning and memory impairments in PPA-induced ASD, highlighting dapagliflozin's potential as an adjunctive therapy for oxidative stress and inflammation-related cognitive decline in ASD. This study underscores the importance of exploring new therapeutic strategies targeting molecular pathways involved in the pathophysiology of ASD, potentially improving the quality of life for individuals affected by this disorder. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc (IVD) degeneration is a multifactorial pathological process resulting in the dysregulation of IVD cell activity. The catabolic shift observed in IVD cells during degeneration leads to increased inflammation, extracellular matrix (ECM) degradation, aberrant intracellular signaling and cell loss. Importantly, these pathological processes are known to be interconnected and to collectively contribute to the progression of the disease. MicroRNAs (miRNAs) are known as strong post-transcriptional regulators, targeting multiple genes simultaneously and regulating numerous intracellular pathways. Specifically, miR-155-5p has been of particular interest since it is known as a pro-inflammatory mediator and contributing factor to diseases like cancer and osteoarthritis. This study investigated the role of miR-155-5p in IVD degeneration with a specific focus on inflammation and mechanosensing. Methods: Gain- and loss-of-function studies were performed through transfection of human Nucleus pulposus (NP) and Annulus fibrosus (AF) cells isolated from degenerated IVDs with miR-155-5p mimics, inhibitors or their corresponding non-targeting control. Transfected cells were then subjected to an inflammatory environment or mechanical loading. Conditioned media and cell lysates were collected for phosphorylation and cytokine secretion arrays as well as gene expression analysis. Results: Increased expression of miR-155-5p in AF cells resulted in significant upregulation of interleukin (IL)-8 cytokine secretion during cyclic stretching and a similar trend in IL-6 secretion during inflammation. Furthermore, miR-155-5p mimics increased the expression of the brain-derived neurotrophic factor (BDNF) in AF cells undergoing cyclic stretching. In NP cells, miR-155-5p gain-of-function resulted in the activation of the mitogen-activated protein kinase (MAPK) signaling pathway through increased phosphorylation of p38 and p53. Lastly, miR-155-5p inhibition caused a significant increase in the anti-inflammatory cytokine IL-10 in AF cells and the tissue inhibitor of metalloproteinases (TIMP)-4 in NP cells respectively. Conclusion: Overall, these results show that miR-155-5p contributes to IVD degeneration by enhancing inflammation through pro-inflammatory cytokines and MAPK signaling, as well as by promoting the catabolic shift of AF cells during mechanical loading. The inhibition of miR-155-5p may constitute a potential therapeutic approach for IVD degeneration and low back pain. [ABSTRACT FROM AUTHOR]

Introduction: Electroconvulsive therapy (ECT) remains a critical intervention for treatment-resistant depression (MDD), yet its neurobiological underpinnings are not fully understood. This pilot study aims to investigate changes in loudness dependence of auditory evoked potentials (LDAEP), a proposed biomarker of serotonergic activity, in patients undergoing ECT. Methods: High-resolution magnetoencephalography (MEG) was utilized to measure LDAEP in nine depressed patients receiving right unilateral ECT. We hypothesized that ECT would reduce the LDAEP slope, reflecting enhanced serotonergic neurotransmission. Depression severity and cognitive performance were assessed using the 24-item Hamilton Depression Rating Scale (HDRS24) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Results: Contrary to our hypothesis, findings indicated a significant increase in LDAEP post-ECT (t8 = 3.17, p = .013). The increase in LDAEP was not associated with changes in depression severity or cognitive performance. Discussion: The observed increase in LDAEP suggests a more complex interaction between ECT and neurobiological systems, rather than a direct reflection of serotonergic neurotransmission. Potential mechanisms for this increase include ECT’s impact on serotonergic, dopaminergic, glutamatergic, and GABAergic receptor activity, neuroplasticity involving brain-derived neurotrophic factor (BDNF), and inflammatory modulators such as TNF-α. Our results highlight the multifaceted effects of ECT on brain function, necessitating further research to elucidate these interactions. [ABSTRACT FROM AUTHOR]

Background: Gestational DNA methylation age (GAmAge) has been developed and validated in European ancestry samples. Its applicability to other ethnicities and associations with fetal stress and newborn phenotypes such as inflammation markers are still to be determined. This study aims to examine the applicability of GAmAge developed from cord blood samples of European decedents to a racially diverse birth cohort, and associations with newborn phenotypes. Methods: GAmAge based on 176 CpGs (Haftorn GAmAge) was calculated for 940 children from a US predominantly urban, low-income, multiethnic birth cohort. Cord blood DNA methylation was profiled by Illumina EPIC array. Newborn phenotypes included anthropometric measurements and, for a subset of newborns (N = 194), twenty-seven cord blood inflammatory markers (sandwich immunoassays). Results: GAmAge had a stronger correlation with GEAA in boys (r = 0.89, 95% confidence interval (CI) [0.87,0.91]) compared with girls (r = 0.83, 95% CI [0.80,0.86]), and was stronger among extremely preterm to very preterm babies (r = 0.91, 95% CI [0.81,0.96]), compared with moderate (r = 0.48, 95% CI [0.34,0.60]) and term babies (r = 0.58, 95% CI [0.53,0.63]). Among White newborns (N = 51), the correlation between GAmAge vs. GEAA was slightly stronger (r = 0.89, 95% CI [0.82,0.94]) compared with Black/African American newborns (N = 668; r = 0.87, 95% CI [0.85,0.89]) or Hispanic (N = 221; r = 0.79, 95% CI [0.74,0.84]). Adjusting for GEAA and sex, GAmAge was associated with anthropometric measurements, cord blood brain-derived neurotrophic factor (BDNF), and monocyte chemoattractant protein-1 (MCP-1) (p < 0.05 for all). Conclusions: GAmAge estimation is robust across different populations and racial/ethnic subgroups. GAmAge may be utilized as a proxy for GEAA and for assessing fetus development, indicated by inflammatory state and birth outcomes. [ABSTRACT FROM AUTHOR]

SH2B1 mutations are associated with obesity, type 2 diabetes, and metabolic dysfunction‐associated steatotic liver disease (MASLD) in humans. Global deletion of Sh2b1 results in severe obesity, type 2 diabetes, and MASLD in mice. Neuron‐specific restoration of SH2B1 rescues the obesity phenotype of Sh2b1‐null mice, indicating that the brain is a main SH2B1 target. However, SH2B1 neurocircuits remain elusive. SH2B1‐expressing neurons in the paraventricular hypothalamus (PVHSH2B1) and a PVHSH2B1→dorsal raphe nucleus (DRN) neurocircuit are identified here. PVHSH2B1 axons monosynaptically innervate DRN neurons. Optogenetic stimulation of PVHSH2B1 axonal fibers in the DRN suppresses food intake. Chronic inhibition of PVHSH2B1 neurons causes obesity. In male and female mice, either embryonic‐onset or adult‐onset deletion of Sh2b1 in PVH neurons causes energy imbalance, obesity, insulin resistance, glucose intolerance, and MASLD. Ablation of Sh2b1 in the DRN‐projecting PVHSH2B1 subpopulation also causes energy imbalance, obesity, and metabolic disorders. Conversely, SH2B1 overexpression in either total or DRN‐projecting PVHSH2B1 neurons protects against diet‐induced obesity. SH2B1 binds to TrkB and enhances brain‐derived neurotrophic factor (BDNF) signaling. Ablation of Sh2b1 in PVHSH2B1 neurons induces BDNF resistance in the PVH, contributing to obesity. In conclusion, these results unveil a previously unrecognized PVHSH2B1→DRN neurocircuit through which SH2B1 defends against obesity by enhancing BDNF/TrkB signaling. [ABSTRACT FROM AUTHOR]

Background: The development of postpartum depression has been linked to fluctuations in the levels of neurotransmitters in the human body, such as 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (Norepinephrine, NE), and brain derived neurotrophic factor (BDNF). Research has indicated that the antidepressant effect of esketamine are mediated by monoamine transmitters and neurotrophic factors. Therefore, we postulate that intravenous administration of esketamine in patients with postpartum depression may alter the serum concentrations of these neurotransmitters. Methods: Three hundred fifteen patients with postpartum depression were selected and divided into two groups based on randomized numerical expression: esketamine (E) group (0. 25 mg/kg esketamine) and control (C) group (a same volume of 0.9% saline), all the drugs were pumped for 40 min. After the end of drug pumping, all patients were continuously observed for 2 h. Changes in serum levels of 5-HT, DA, NE, BDNF were recorded before drug administration and on the 3rd day after drug administration. The scores of Edinburgh Postnatal Depression Scale (EPDS) were calculated before drug administration, and on the 3rd day and on the 30th day after drug administration. Dizziness, headache, nausea, vomiting, drowsiness, and feeling of detachment occurred were recorded within 2 h after drug administration. Results: Before drug administration, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (0. 91 ± 0. 19 vs. 0. 98 ± 0. 21, P = 0. 181), (2. 38 ± 0. 35 vs. 2. 32 ± 0. 32, P = 0. 491), (3. 07 ± 0. 89 vs 3. 02 ± 0. 88, P = 0. 828), (39. 79 ± 7. 78 vs 41. 34 ± 10. 03, P = 0. 506). On the third day post-medication, the serum concentrations of 5-HT,DA,BDNF,NE in Group E and Group C were namely (1. 42 ± 0. 35 vs. 0. 96 ± 0. 24, P < 0. 001), (3. 99 ± 0. 17 vs. 2. 41 ± 0. 28, P < 0. 001),(5. 45 ± 0. 81 vs 3. 22 ± 0. 76, P < 0. 001),(44. 36 ± 9. 98 vs 40. 69 ± 11. 75, P = 0. 198). Before medication, the EPDS scores were (16. 15 ± 3. 02 vs 17. 85 ± 3. 89, P = 0. 064). on the third day after medication, the Group E had significantly reduced scores (12. 98 ± 2. 39 vs 16. 73 ± 3. 52, P < 0. 001). On the 30rd day after medication, EPDS scores between the two groups were (16. 34 ± 3. 43 vs 16. 91 ± 4. 02, p = 0. 203). Within 2 h of medication, the rate of adverse events was similar between the two groups. Conclusions: Small doses of esketamine can increase the serum concentration of 5-HT,DA,BDNF, and in the short term, decrease EPDS scores, and improve postpartum depressive symptoms. Trial registration: Retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2300078343, 2023/12/05). [ABSTRACT FROM AUTHOR]

Background: Depression is a chronic psychiatric condition that places significant burdens on individuals, families, and societies. The rapid evolution of non-invasive brain stimulation techniques has facilitated the extensive clinical use of Transcranial Magnetic Stimulation (TMS) for depression treatment. In light of the substantial recent increase in related research, this study aims to employ bibliometric methods to systematically review the global research status and trends of TMS in depression, providing a reference and guiding future studies in this field. Methods: We retrieved literature on TMS and depression published between 1999 and 2023 from the Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) databases within the Web of Science Core Collection (WoSCC). Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps. Results: A total of 5,046 publications were extracted covering the period from 1999 to 2023 in the field of TMS and depression. The publication output exhibited an overall exponential growth trend. These articles were published across 804 different journals, BRAIN STIMULATION is the platform that receives the most articles in this area. The literature involved contributions from over 16,000 authors affiliated with 4,573 institutions across 77 countries. The United States contributed the largest number of publications, with the University of Toronto and Daskalakis ZJ leading as the most prolific institution and author, respectively. Keywords such as "Default Mode Network," "Functional Connectivity," and "Theta Burst" have recently garnered significant attention. Research in this field primarily focuses on TMS stimulation patterns, their therapeutic efficacy and safety, brain region and network mechanisms under combined brain imaging technologies, and the modulation effects of TMS on brain-derived neurotrophic factor (BDNF) and neurotransmitter levels. Conclusion: In recent years, TMS therapy has demonstrated extensive potential applications and significant implications for the treatment of depression. Research in the field of TMS for depression has achieved notable progress. Particularly, the development of novel TMS stimulation patterns and the integration of TMS therapy with multimodal techniques and machine learning algorithms for precision treatment and investigation of brain network mechanisms have emerged as current research hotspots. [ABSTRACT FROM AUTHOR]

A large body of evidence implies the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorders (ASDs). A deficiency of BDNF in the hippocampus and frontal cortex of BTBR mice (a model of autism) has been noted in a number of studies. Earlier, we showed that induction of BDNF overexpression in the hippocampus of BTBR mice reduced anxiety and severity of stereotyped behavior, but did not affect social interest. Here, we induced BDNF overexpression in the frontal cortex neurons of BTBR mice using an adeno-associated viral vector, which resulted in a significant increase in the social interest in the three-chamber social test. At the same time, the stereotypy, exploratory behavior, anxiety-like behavior, and novel object recognition were not affected. Therefore, we have shown for the first time that the presence of BDNF in the frontal cortex is critical for the expression of social interest in BTBR mice, since compensation for its deficiency in this structure eliminated the autism-like deficiencies in the social behavior characteristic for these animals. [ABSTRACT FROM AUTHOR]

Background: Vascular diseases, including atherosclerotic cardiovascular disease (ASCVD) and stroke, increase the risk of Alzheimer's disease and cognitive impairment. Serum biomarkers, such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1), may be indicators of cognitive health. Objective: We examined whether vascular risk was associated with levels of cognition and serum biomarkers in older women with cardiovascular disease (CVD). Methods: Baseline data from a lifestyle trial in older women (n = 253) with CVD (NCT04556305) were analyzed. Vascular risk scores were calculated for ASCVD (ASCVD risk estimator) and stroke (CHA2DS2-VASc) based on published criteria. Cognition-related serum biomarkers included BDNF, VEGF, and IGF-1. Cognition was based on a battery of neuropsychological tests that assessed episodic memory, semantic memory, working memory, and executive function. A series of separate linear regression models were used to evaluate associations of vascular risk scores with outcomes of cognition and serum biomarkers. All models were adjusted for age, education level, and racial and ethnic background. Results: In separate linear regression models, both ASCVD and CHA2DS2-VASc scores were inversely associated with semantic memory (β= –0.22, p = 0.007 and β= –0.15, p = 0.022, respectively), with no significant findings for the other cognitive domains. There were no significant associations between vascular risk scores and serum biomarkers. Conclusions: Future studies should prospectively examine associations between vascular risk and cognition in other populations and additionally consider other serum biomarkers that may be related to vascular risk and cognition. [ABSTRACT FROM AUTHOR]

The first systematic reviews of the effects of exercise on appetite‐regulation and energy intake demonstrated changes in appetite‐regulating hormones consistent with appetite suppression and decreases in subsequent relative energy intake over a decade ago. More recently, an intensity‐dependent effect and several potential mechanisms were proposed, and this review aims to highlight advances in this field. While exercise‐induced appetite suppression clearly involves acylated ghrelin, glucagon‐like peptide‐1 may also be involved, though recent evidence suggests peptide tyrosine tyrosine may not be relevant. Changes in subjective appetite perceptions and energy intake continue to be equivocal, though these results are likely due to small sample sizes and methodological inconsistencies. Of the proposed mechanisms responsible for exercise‐induced appetite suppression, lactate has garnered the most support through in vitro and in vivo rodent studies as well as a growing amount of work in humans. Other potential modulators of exercise‐induced appetite suppression may include sex hormones, growth‐differentiation factor 15, Lac‐Phe, brain‐derived neurotrophic factor, and asprosin. Research should focus on the mechanisms responsible for the changes and consider these other modulators (i.e., myokines/exerkines) of appetite to improve our understanding of the role of exercise on appetite regulation. [ABSTRACT FROM AUTHOR]

Brain‐derived neurotrophic factor (BDNF) content and signaling has been identified as one potential regulator of amyloid precursor protein (APP) processing. Recently published work has demonstrated that BDNF reduces BACE1 activity while also elevating the inhibition of GSK3β in the prefrontal cortex of male C57BL/6J mice. These results provide evidence that BDNF alters APP processing by reducing BACE1 activity, which may act through GSK3β inhibition. The purpose of this study was to further explore the role of GSK3β in BDNF‐induced regulation on BACE1 activity. We utilized a cell culture and an in vitro activity assay model to pharmacologically target BDNF and GSK3β signaling to confirm its involvement in the BDNF response. Treatment of differentiated SH‐SY5Y neuronal cells with 75 ng/mL BDNF resulted in elevated pTrkB content, pAkt content, pGSK3β content, and reduced BACE1 activity. An in vitro BACE1 activity assay utilizing mouse prefrontal cortex (n = 6/group) supplemented with BDNF, BDNF + ANA12 (Trkb antagonist), or BDNF + wortmannin (Akt inhibitor) demonstrated that BDNF reduced BACE1 activity; however, in the presence of TrkB or Akt inhibition, this effect was abolished. An in vitro ADAM10 activity assay utilizing mouse prefrontal cortex (n = 6/group) supplemented with BDNF, BDNF + ANA12 (Trkb antagonist), or BDNF + wortmannin (Akt inhibitor) demonstrated that BDNF did not alter ADAM10 activity. However, inhibiting BDNF signaling reduced ADAM10 activity. Collectively these studies suggest that GSK3β inhibition may be necessary for BDNF‐induced reductions in BACE1 activity. These findings will allow for the optimization of future therapeutic strategies by selectively targeting TrkB activation and GSK3β inhibition. [ABSTRACT FROM AUTHOR]

To evaluate the role of brain-derived neurotrophic factor (BDNF)—a crucial modulator of neural development and plasticity—in the association between prenatal maternal anxiety, depression, and perceived stress and child neurodevelopment in a prospective cohort study. We included 526 eligible mother-child pairs from the Shanghai Birth Cohort in the study. Maternal mental health was assessed at mid-pregnancy using Zung's Self-Rating Anxiety Scale, Center for Epidemiologic Studies Depression Scale, and Perceived Stress Scale. The concentration of BDNF in cord blood was measured by ELISA. The offspring neurodevelopment at 24 months of age was assessed using the Bayley Scales. Linear and non-linear regression models were used. The average cord blood BDNF levels were higher in female newborns and those born via vaginal delivery, full term, and normal birth weight. Prenatal maternal anxiety (β = −0.32; 95 % CI: −0.55, −0.09), depression (β = −0.30; 95 % CI: −0.52, −0.08), and perceived stress (β = −0.41; 95 % CI: −0.71, −0.12) scores were negatively associated with social-emotional performance at 24 months of age. However, no significant associations were found between prenatal maternal anxiety, depression, or perceived stress at mid-pregnancy and cord blood BDNF levels, as well as between cord blood BDNF levels and child neurodevelopment. Maternal mental health at different timepoints during pregnancy and generalizability of the results warrant further assessment. Prenatal mental health was not associated with cord blood BDNF level and that BDNF may not be a mediator in the association between prenatal mental health and child neurodevelopment. • No statistically significant correlations were found between prenatal maternal mental health and cord blood BDNF levels. • BDNF was not associated with neurodevelopment in 2-year-olds, except for a non-linear relationship with the cognitive domain. • BDNF may not mediate the link between maternal mental health during pregnancy and early childhood neurodevelopment. [ABSTRACT FROM AUTHOR]

Simple Summary: In this work, we documented the presence of two neurotrophins NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) in the pancreas of two species of marine mammals, Tursiops truncatus (common bottlenose dolphin) and Otaria flavescens (South American sea lion). Pancreas samples were provided by the Mediterranean Marine Mammal Tissue Bank of the Department of Comparative Biomedicine and Food Science of the University of Padua (Italy). These two growth factors are well-known mediators for maintaining the survival of neurons but also exert a metabotrophic effect. The localization in the pancreas of bottlenose dolphins and sea lions of these neurotrophins could help to better understand how these marine animals handle metabolic challenges in their adaptation to ocean life. In this study, we have investigated the immunolocalization of NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor) in the pancreas of two species of marine mammals: Tursiops truncatus (common bottlenose dolphin), belonging to the order of the Artiodactyla, and Otaria flavescens (South American sea lion), belonging to the order of the Carnivora. Our results demonstrated a significant presence of NGF and BDNF in the pancreas of both species with a wide distribution pattern observed in the exocrine and endocrine components. We identified some differences that can be attributed to the different feeding habits of the two species, which possess a different morphological organization of the digestive system. Altogether, these preliminary observations open new perspectives on the function of neurotrophins and the adaptive mechanisms of marine mammals in the aquatic environment, suggesting potential parallels between the physiology of marine and terrestrial mammals. [ABSTRACT FROM AUTHOR]

Microglia respond to stressors by secreting cytokines or growth factors, playing a crucial role in maintaining brain homeostasis. While the antidepressant-like effects of Polygonatum sibiricum polysaccharides (PSPs) have been observed in mice, their potential effectiveness involving microglial regulation remains unknown. This study investigates the antidepressant-like mechanism of PSP by regulating microglial phenotype and signaling pathways in the prefrontal cortex of chronic restraint stress (CRS)-induced mice. PSP was extracted, purified, characterized, and orally administered to CRS mice. High-performance gel permeation chromatography (HPGPC) revealed that PSP has a molecular weight of 5.6 kDa. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that PSP exhibited a layered structure with densely packed, irregular surfaces. PSP treatment significantly increased sucrose preference (low: 71%, p < 0.01; medium: 69%, p < 0.05; high: 75%, p < 0.001 vs. CRS: 58%) and reduced immobility time (low: 74 s, p < 0.01; medium: 68 s, p < 0.01; high: 79 s, p < 0.05 vs. CRS: 129 s), indicating the alleviation of depressive-like behaviors. PSP inhibited microglial activation (PSP, 131/mm2 vs. CRS, 173/mm2, p = 0.057), reversing CRS-induced microglial hypertrophy and hyper-ramification. Furthermore, PSP inactivated microglial activation by inhibiting NLRP3/ASC/caspase-1/IL-1β signaling pathways, increasing BDNF synthesis and activating brain-derived neurotrophic factor (BDNF)-mediated neurogenesis (PSP, 80/per DG vs. CRS, 49/per DG, p < 0.01). In conclusion, PSP exerts antidepressant-like effects through the regulation of microglial activity and neuroinflammatory pathways, indicating it as a potential natural compound for depression treatment. [ABSTRACT FROM AUTHOR]

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA targets to achieve these effects have not been widely explored. Here, we tested the effects of OEA treatment during alcohol SA, extinction or previous to cue-induced reinstatement of alcohol seeking. In addition, we measured gene expression changes in the striatum and hippocampus of relevant receptors for alcohol consumption (Drd1, Drd2, Cnr1, Oprm) as well as immune-related proteins (Il-6, Il-1β, Tlr4) and the brain-derived neurotrophic factor (Bdnf). Our results confirmed that when administered contingently, systemic OEA administration reduced alcohol SA and attenuated cue-induced reinstatement. Interestingly, we also observed that OEA treatment reduced the number of sessions needed for the extinction of alcohol seeking. Biochemical analyses showed that OEA induced gene expression changes in dopamine and cannabinoid receptors in the striatum and hippocampus. In addition, OEA treatment modulated the long-term immune response and increased Bdnf expression. These results suggest that boosting OEA levels may be an effective strategy for reducing alcohol SA and preventing relapse. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease that involves modified low-density lipoproteins (LDL) which play a pivotal role in the initiation and progression of the disease. Myeloperoxidase oxidized LDL (Mox-LDL) is considered to be the most patho-physiologically relevant type of modified LDL and has been reported to be ubiquitously present in atheroma plaques of patients with atherosclerosis. Besides its involvement in the latter disease state, Mox-LDL has also been shown to be implicated in the pathogenesis of various illnesses including sleep disorders, which are in turn associated with heart disease and depression in many intricate ways. Meanwhile, we have recently shown that lox-1-mediated Mox-LDL signaling modulates neuroserpin activity in endothelial cells, which could have major implications that go beyond the pathophysiology of stroke and cerebrovascular disease (CD). Of note is that tissue plasminogen activator (tPA), which is the main target of neuroserpin in the brain, has a crucial function in the processing of brain-derived neurotrophic factor (BDNF) into its mature form. This factor is known to be involved in major depressive disorder (MDD) development and pathogenesis. Since tPA is more conventionally recognized as being involved in fibrinolytic mechanisms, and its effect on the BDNF system in the context of MDD is still not extensively studied, we speculate that any Mox-LDL-driven change in the activity of tPA in patients with atherosclerosis may lead to a decrease in the production of mature BDNF, resulting in impaired neural plasticity and depression. Deciphering the mechanisms of interaction between those factors could help in better understanding the potentially overlapping pathological mechanisms that regulate disease processes in CD and MDD, supporting the possibility of novel and common therapeutic opportunities for millions of patients worldwide. [ABSTRACT FROM AUTHOR]

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain, and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis. [ABSTRACT FROM AUTHOR]

Scars may represent more than a cosmetic concern for patients; they may impose functional limitations and are frequently associated with the sensation of itching or pain, thus impacting both psychological and physical well-being. From an aesthetic perspective, scars display variances in color, thickness, texture, contour, and their homogeneity, while the functional aspect encompasses considerations of functionality, pliability, and sensory perception. Scars located in critical anatomic areas have the potential to induce profound impairments, including contracture-related mobility restrictions, thereby significantly impacting daily functioning and the quality of life. Conventional approaches to scar management may suffice to a certain extent, yet there are cases where tailored interventions are warranted. Autologous fat grafting emerges as a promising therapeutic avenue in such instances. Fundamental mechanisms underlying scar formation include chronic inflammation, fibrogenesis and dysregulated wound healing, among other contributing factors. These mechanisms can potentially be alleviated through the application of adipose-derived stem cells, which represent the principal cellular component utilized in the process of lipofilling. Adipose-derived stem cells possess the capacity to secrete proangiogenic factors such as fibroblast growth factor, vascular endothelial growth factor and hepatocyte growth factor, as well as neurotrophic factors, such as brain-derived neurotrophic factors. Moreover, they exhibit multipotency, remodel the extracellular matrix, act in a paracrine manner, and exert immunomodulatory effects through cytokine secretion. These molecular processes contribute to neoangiogenesis, the alleviation of chronic inflammation, and the promotion of a conducive milieu for wound healing. Beyond the obvious benefit in restoring volume, the adipose-derived stem cells and their regenerative capacities facilitate a reduction in pain, pruritus, and fibrosis. This review elucidates the regenerative potential of autologous fat grafting and its beneficial and promising effects on both functional and aesthetic outcomes when applied to scar tissue. [ABSTRACT FROM AUTHOR]

Background: Neuroplasticity as a mechanism to overcome central nervous system injury resulting from different neurological diseases has gained increasing attention in recent years. However, deficiency of these repair mechanisms leads to the accumulation of neuronal damage and therefore long-term disability. To date, the mechanisms by which remyelination occurs and why the extent of remyelination differs interindividually between multiple sclerosis patients regardless of the disease course are unclear. A member of the neurotrophins family, the brain-derived neurotrophic factor (BDNF) has received particular attention in this context as it is thought to play a central role in remyelination and thus neuroplasticity, neuroprotection, and memory. Objective: To analyse the current literature regarding BDNF in different areas of multiple sclerosis and to provide an overview of the current state of knowledge in this field. Conclusion: To date, studies assessing the role of BDNF in patients with multiple sclerosis remain inconclusive. However, there is emerging evidence for a beneficial effect of BDNF in multiple sclerosis, as studies reporting positive effects on clinical as well as MRI characteristics outweighed studies assuming detrimental effects of BDNF. Furthermore, studies regarding the Val66Met polymorphism have not conclusively determined whether this is a protective or harmful factor in multiple sclerosis, but again most studies hypothesized a protective effect through modulation of BDNF secretion and anti-inflammatory effects with different effects in healthy controls and patients with multiple sclerosis, possibly due to the pro-inflammatory milieu in patients with multiple sclerosis. Further studies with larger cohorts and longitudinal follow-ups are needed to improve our understanding of the effects of BDNF in the central nervous system, especially in the context of multiple sclerosis. [ABSTRACT FROM AUTHOR]

This article explores the role of potassium channels in animal models of post-traumatic stress disorder (PTSD) and their potential therapeutic implications. Potassium channels are important in regulating brain function and have been associated with various neuropsychiatric disorders. Animal models have shown that different types of potassium channels play a role in fear-related behaviors and memory. Genome-wide association studies have identified genes involved in fear and stress responses that may contribute to vulnerability to PTSD. Specific potassium channel subtypes have been implicated in the development of certain PTSD symptoms and may be potential targets for treatment. Activation or inhibition of these channels can affect fear responses and consolidation of fear memories. The article acknowledges the need for further research in humans and the limitations of the available evidence. The document provides a list of references for library patrons conducting research on the neurobiology of fear and PTSD, covering topics such as ion channels, pharmacological interventions, and genetic factors associated with PTSD. [Extracted from the article]

Introduction: Probiotics have been recognized for their various biological activities, including antioxidant and anti-inflammatory properties. This study investigates the therapeutic effect of a novel probiotic formula, BLLL, consisting of Bifidobacterium breve, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus helveticus, on chronic stress-induced depressionlike behaviors in mice. Methods: The BLLL formula or phosphate-buffered saline (PBS) was given orally at a dose of 2, 4, or 8 x 1010 CFU/kg once daily for 10 days in mice treated with chronic unpredictable stress (CUS) treated or vehicle. Depression-like behaviors were assessed using the sucrose preference test (SPT), the forced swimming test (FST), and the tail suspension test (TST). The mRNA and/or protein expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), IL-4, IL-10, and chitinase-3-like protein 3 (CHI3L1, also known as Ym-1), as well as the concentration of nitrite, malondialdehyde (MDA), glutathione (GSH), and brainderived neurotrophic factor (BDNF) in the hippocampus and medial prefrontal cortex were examined. Results: The BLLL formula treatment at a dose of 8 x 1010 CFU/kg, but not at a dose of 2 or 4 x 1010 CFU/kg, improved CUS-induced depression-like behaviors in mice, as shown by the decrease in immobility time in the TST and FST and the increase in sucrose intake in the SPT. Further analysis revealed that BLLL treatment suppressed the CUS-induced increase in IL-1β, IL-6, and TNF-α mRNA and protein levels, as well as the CUS-induced decrease in IL-4, IL-10, and Ym-1 mRNA and/or protein levels in the hippocampus and medial prefrontal cortex. In addition, treatment with the BLLL formula countered the CUS-induced increase in nitrite and MDA levels and the CUS-induced decrease in GSH content and BDNF concentration in the hippocampus and medial prefrontal cortex. Conclusion: These results demonstrate that the novel probiotic formula BLLL ameliorates chronic stress-induced depression-like behavior in mice by suppressing neuroinflammation and oxido-nitrosative stress in the brain. [ABSTRACT FROM AUTHOR]

Biotin and arginine play crucial roles in lipid metabolism and may offer promising interventions against obesity. This study examined the combined effect of magnesium biotinate (MgB) and inositol-stabilized arginine silicate complex (ASI) on obesity-related oxidative imbalance, inflammation, lipid metabolism and neuromodulation in rats on a high-fat diet (HFD). Forty rats were divided into five groups: (a) control: rats were fed a standard diet containing 12% of energy from fat; (b) HFD: rats were fed the HFD with 42% of energy from fat; (c) HFD + MgB: rats were fed the HFD and given 0.31 mg/kg body weight (BW) MgB, (d) HFD + ASI: rats were fed the HFD and were given 12.91 mg/kg BW ASI), and (e) HFD + MgB + ASI: rats were fed the HFD and given 0.31 mg/kg BW MgB and 12.91 mg/kg BW ASI). The combined administration of MgB and ASI reduced the levels of serum cholesterol, free fatty acid (FFA), and malondialdehyde (MDA), as well as liver inflammatory cytokines, sterol regulatory element-binding protein 1-c (SREBP-1c), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) proteins (P < 0.001) compared to HFD rats without supplementation. Moreover, this combination increased the activities of antioxidant enzymes (P < 0.05) and boosted the brain-derived neurotrophic factor (BDNF), serotonin, dopamine (P < 0.001), as well as liver insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < 0.001). These findings suggest that combining MgB and ASI could deter liver fat accumulation and enhance lipid metabolism in HFD-fed rats by modulating various metabolic pathways and neuromodulators related to energy metabolism. This combination demonstrates potential in addressing obesity and its related metabolic dysfunctions. [ABSTRACT FROM AUTHOR]

The neurotrophic growth factor brain‐derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24 h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24 h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady‐state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments. [ABSTRACT FROM AUTHOR]