Brain-derived Neurotrophic Factor Levels Research Articles

Dynamic changes in the hippocampal memory index and biochemical indices in Sprague Dawley rats exposed to intrauterine kola nut.

Kola nut is commonly consumed by pregnant women to suppress symptoms of morning sickness. This study investigated the effects of kola nut on the biochemical indices of the hippocampus and its dependent memory. Kola nut extract was fed to pregnant dams from the first day of their pregnancy until parturition. The following behavioral function tests were conducted: surface righting (SR); cliff avoidance (post-natal day [PND] 4, 5, 6 & 7); open field; novel object recognition and location; and radial-arm maze (PND 21 and 56). The levels of brain-derived neurotrophic factor (BDNF), acetylcholine (ACh), and malondialdehyde (MDA) of the matched hippocampal tissues were also checked in the pups. The kola nut-treated pups showed significantly reduced behavioral indices compared to the pups in the control group: lower postural balance, higher risk avoidance memory, and lower frequency in pivoting and rearing compared to that in the control group. However, the frequency of urine and fecal bolus was significantly lower in the pups in the control group than that in the treated pups. The discrimination ratio of the control group pups in novel object recognition (NOR) and novel object location (NOL) was significantly higher than that in the treated pups, and the time taken by the treated pups to complete RAM was significantly higher. The levels of ACh and BDNF in the treated pups were increased compared to that in control pups. A positive correlation was found between MDA and SR (r = 0.7207; p = 0.0437), grooming (r = 0.7707; p = 0.0252), and fecal bolus (r = 0.7606; p = 0.0284), as well as with the BDNF level in those treated with grooming (r = 0.7570; p = 0.0297). However, negative correlations between ACh and rearing (r = -0.8261; p = 0.0115) and fecal bolus (r = -0.8066; p = 0.0156) and a positive correlation with NOL (r = 0.8358; p = 0.0098) were observed. Based on these observations, the study concluded that Kola nut affects both biochemical and hippocampal memory profiles.

The Effect of Psilocybe cubensis on Spatial Memory and BDNF Expression in Male Rats Exposed to Chronic Unpredictable Mild Stress

ABSTRACT Psilocybin-containing mushrooms, commonly known as magic mushrooms, drastically affect mental processing, cognitive functioning, and the mood state. In the present study, we investigated the effect of the Psilocybe cubensis extract on spatial memory and the brain-derived neurotrophic factor (BDNF) in rats exposed to chronic unpredictable mild stress (CUMS). The duration of CUMS was 4 weeks. Spatial learning and memory were measured using the Morris water maze apparatus. The Psilocybe cubensis extract was intraperitoneally injected (20 mg/kg) in different time periods: 5 min before training, 24 h before training, 48 h before training, 5 min after training, and 5 min before the probe test. Results showed that CUMS impaired spatial learning and memory, and decreased BDNF in the hippocampus. Psilocybe cubensis (24 and 48 h before training) restored spatial learning, while (48 h before training) restored spatial memory impairment in CUMS rats. Psilocybe cubensis (24 and 48 h before training) increased BDNF in CUMS rats. Psilocybe cubensis administrations (expect 48 h before training) impaired spatial learning and memory and decreased BDNF levels in controls. In conclusion, we suggested that Psilocybe cubensis may be beneficial for the improvement of memory deficits induced by CUMS, while the time of injection seems to be an important factor in its final effect.

Exploring the impact of childhood maltreatment on epigenetic and brain-derived neurotrophic factor changes in bipolar disorder and healthy control.

Childhood maltreatment may be linked to epigenetics and brain-derived neurotrophic factor (BDNF) changes, which are mechanisms altered in several psychiatric conditions, including bipolar disorder (BD). However, the specific mechanisms connecting childhood maltreatment to the pathophysiology of BD remain unclear. The present study aims to examine the effects of childhood maltreatment on epigenetic and neurotrophic outcomes in BD patients and health controls. History of childhood maltreatment was obtained using the Childhood Trauma Questionnaire (CTQ) from 36 BD outpatients and 46 healthy subjects. DNA methyltransferase (DNMT) activity, HMTH3K9 activity, histone 3 lysine 9 tri-methylation (H3K9me3) levels, histone deacetylase (HDAC)1 levels, HDAC2 levels, histone 3 lysine 14 acetylation (H3K14ac) levels, and mRNA of BDNF were evaluated in peripheral blood mononuclear cells. Plasma BDNF levels were also measured. Total scores of CTQ, as well as the subscale scores of emotional abuse, sexual abuse, and emotional neglect, were predictive of changes in DNMT and HMTh3k9 activity, H3K9m3 levels, BDNF mRNA expression, and BDNF levels. These findings were observed in all our samples and, in some cases, among BD patients. Emotional abuse was the main childhood maltreatment subtype associated with epigenetic alterations in BD. Our results elucidate some mechanisms by which childhood maltreatment can alter epigenetic and neurotrophic markers. Especially in BD subjects, our results suggest childhood maltreatment per se is not a direct cause for epigenetic alterations. In another way, we suppose that the effect of childhood maltreatment could be cumulative and interact with other factors associated with the pathophysiology of BD.

ACSL3 is a promising therapeutic target for alleviating anxiety and depression in Alzheimer's disease.

Alzheimer's disease (AD), the leading cause of dementia, affects over 55 million people worldwide and is often accompanied by depression and anxiety. Both significantly impact patients' quality of life and impose substantial societal and economic burdens on healthcare systems. Identifying the complex regulatory mechanisms that contribute to the psychological and emotional deficits in AD will provide promising therapeutic targets. Biosynthesis of omega-3 (ω3) and omega-6 fatty acids (ω6-FA) through long-chain acyl-CoA synthetases (ACSL) is crucial for cell function and survival. This is due to ω3/6-FA's imperative role in modulating the plasma membrane, energy production, and inflammation. While ACSL dysfunction is known to cause heart, liver, and kidney diseases, the role of ACSL in pathological conditions in the central nervous system (e.g., depression and anxiety) remains largely unexplored. The impact of ACSLs on AD-related depression and anxiety was investigated in a mouse model of Alzheimer's disease (3xTg-AD). ACSL3 levels were significantly reduced in the hippocampus of aged 3xTg-AD mice (via capillary-based immunoassay). This reduction in ACAL3 was closely associated with increased depression and anxiety-like behavior (via forced swim, tail suspension, elevated plus maze, and sucrose preference test). Upregulation of ACSL3 via adenovirus in aged 3xTg-AD mice led to increased protein levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor C (VEGF-C) (via brain histology, capillary-based immunoassay), resulting in alleviation of depression and anxiety symptoms. The present study highlights a novel neuroprotective role of ACSL3 in the brain. Targeting ACSL3 will offer an innovative approach for treating AD-related depression and anxiety.

The Effects of Curcumin on Brain-Derived Neurotrophic Factor Expression in Neurodegenerative Disorders.

Brain-Derived Neurotrophic Factor (BDNF) is a crucial molecule implicated in plastic modifications related to learning and memory. The expression of BDNF is highly regulated, which can lead to significant variability in BDNF levels in healthy subjects. Changes in BDNF expression might be associated with neuropsychiatric diseases, particularly in structures important for memory processes, including the hippocampus and parahippocampal areas. Curcumin is a natural polyphenolic compound that has great potential for the prevention and treatment of age-related disorders by regulating and activating the expression of neural protective proteins such as BDNF. This review discusses and analyzes the available scientific literature on the effects of curcumin on BDNF production and function in both in vitro and in vivo models of disease.

Association Between the Enriched Environment Level and Serum Brain-Derived Neurotrophic Factor (BDNF) in Patients with Major Depressive Disorder

Major Depressive Disorder (MDD) is a neuropsychiatric condition whose neurobiological characteristics include alterations in brain plasticity, modulated by Brain-Derived Neurotrophic Factor (BDNF). In animal models, environmental enrichment promotes neuroplasticity and reduces depressive-like behaviors. In humans, we proposed to assess the level of Enriched Environment (EE) using a questionnaire that includes different domains of the EE (cognitive, social, and physical), which we named the EE Indicator (EEI). Objective: To determine the relationship between the level of EE and serum BDNF in participants with MDD and healthy controls. Materials: Participants with MDD without antidepressant treatment and healthy controls were recruited, and their EE level and serum BDNF concentration were determined looking for correlations between their clinical characteristics and the cognitive, social, and physical activities according to the EEI. Results: A total of 25 participants were recruited, of which 6 participants with MDD and the same number of controls were selected in a paired manner. Although no differences were found in the concentration of BDNF between the groups, positive correlations were observed between cognitive EE and BDNF (r = 0.62, p = 0.035), as well as negative social EE and the Hamilton Depression Rating Scale (HDRS) (r = −0.86, p = 0.001). The sum between cognitive and social EE showed a positive correlation with the serum concentration of BDNF (r = 0.34, p = 0.0451). Conclusions: The level of EE is potentially modulating the presence and severity of MDD at a clinical level, but it can also influence at a neuroplastic level through promoting or limiting the concentration of BDNF.

Peripheral molecular and brain structural profile implicated stress activation and hyperoxidation in methamphetamine use disorder.

Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction. In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme-linked immunosorbent assay. The overall molecular disruption caused by methamphetamine was inversely related to withdrawal time (P = 0.0008), with partial recovery observed after 1 year of follow-up (P = 2.20 × 10-5). Molecules related to stress, immune activation, oxidative products, and cardiac injury were significantly elevated in all MUD groups, while antioxidation enzymes were downregulated. Additionally, the blood level of brain-derived neurotrophic factor was significantly correlated with gray matter volumes in nine brain regions (fusiform gyrus, orbitofrontal cortex, temporal pole, caudate, cerebellum crus, and vermis, adjusted P < 0.05) among patients with MUD. These findings suggest that patients with MUD exhibit elevated levels of immune response, stress, and oxidative stress, which are associated with brain structural abnormalities.

KDM4A facilitates neuropathic pain and microglial M1 polarization by regulating BDNF in a rat model of brachial plexus avulsion

BackgroundMany patients with brachial plexus avulsion (BPA) suffer from neuropathic pain, but the mechanism remains elusive. Modifications of histones, the proteins responsible for organizing DNA, may play an important role...

Role of Cardiovascular Risk in Associations of Brain-Derived Neurotrophic Factor with Longitudinal Brain and Cognitive Trajectories in Older Adults

ABSTRACT Background Higher levels of brain-derived neurotrophic factor (BDNF) have been associated with better neurocognitive outcomes. BDNF is present in cardiovascular tissue, and some evidence suggests it may benefit cardiovascular function. The current study assessed whether there is a mediating and/or moderating role of cardiovascular health in the relationship between BDNF and brain and cognitive outcomes. Method We examined longitudinal data from 397 older adults (aged 54–89;164 females, 233 males) enrolled in the Alzheimer’s Disease Neuroimaging Initiative with available plasma BDNF, medical, neuroimaging, and cognitive assessments. We used path analysis and linear regression to estimate the mediating and moderating roles of two measures of cardiovascular health, the Framingham Risk Score (FRS) and pulse pressure, in the relationships between BDNF and longitudinal changes in brain structure (white matter hyperintensity volume, hippocampal volume, and primary visual cortex volume) and cognitive function (executive function, episodic memory, and language). Results There was no significant association of plasma BDNF with FRS or pulse pressure (ps > 0.31), precluding mediation. There were no robust associations between BDNF and longitudinal change in any brain structural or cognitive measures (ps > .12). Higher FRS was significantly associated with greater increases in WMH volume (ps < .01). FRS and pulse pressure were not associated with any other brain structural or cognitive outcomes (ps > .07). Conclusion These results suggest that cardiovascular health may not play an important role in the influence of BDNF on neurocognitive health in older adults.

The Effect of Two Somatic-Based Practices Dance and Martial Arts on Irisin, BDNF Levels and Cognitive and Physical Fitness in Older Adults: A Randomized Control Trial.

Maintaining healthy brain function during ageing is of great importance, especially for the self-sufficiency of older adults. The main aim of this study was to determine the effects of dance and martial arts on exerkines Brain Derived Neurotrophic Factor (BDNF) and irisin blood serum levels. This randomized controlled trial examined the effects of dance and martial arts on serum Brain-Derived Neurotrophic Factor (BDNF) and irisin levels, as well as cognitive function, mood, and physical measures in older adults. Seventy-seven independently living older adults (mean age 70.3±3.8 years) were randomized into three groups: dance (DG), martial arts (MaG), and control (CG), followed over 12weeks. Generalized linear models were used to assess the interventions' effects. There was a significant increase in BDNF levels in both the DG (1.8 ± 4.9, p < 0.05) and MaG (3.5 ± 6.3, p < 0.05), while CG experienced a decrease (-4.9 ± 8.2, p < 0.05). Between-group effects were significant for BDNF, with DG and MaG showing higher levels than CG (p < 0.05). No significant changes in irisin levels were found. Cognitive performance, particularly attention and mental flexibility (measured by the Trail Making Test A and B), significantly improved in the DG compared to CG (p < 0.05). Additionally, participants in DG showed improved mood based on the Geriatric Depression Scale (p < 0.05) compared to CG. Anthropometric T-scores were significantly associated with changes in irisin levels (p < 0.05) after intervention. The study found that dance and martial arts upregulated BDNF levels, with dance showing notable improvements in cognitive function and mood in older adults. Changes in anthropometric measures were linked to increased irisin levels. These findings suggest that both dance and martial arts may promote healthy brain function in aging populations. NCT05363228.

BDNF and Cerebellar Ataxia.

Brain-derived neurotrophic factor (BDNF) has been proposed as a treatment for neurodegeneration, including diseases of the cerebellum, where BDNF levels or those of its main receptor, TrkB, are often diminished relative to controls, thereby serving as replacement therapy. Experimental evidence indicates that BDNF signaling countered cerebellar degeneration, sensorimotor deficits, or both, in transgenic ATXN1 mice mutated for ataxin-1, Cacna1a knock-in mice mutated for ataxin-6, mice injected with lentivectors encoding RNA sequences against human FXN into the cerebellar cortex, Kcnj6Wv (Weaver) mutant mice with granule cell degeneration, and rats with olivocerebellar transaction, similar to a BDNF-overexpressing transgenic line interbred with Cacng2stg mutant mice. In this regard, this study discusses whether BDNF is effective in cerebellar pathologies where BDNF levels are normal and whether it is effective in cases with combined cerebellar and basal ganglia damage.

Neonatal Maternal Separation Impairs Cognitive Function and Synaptic Plasticity in Adult Male CD-1 Mice

Maternal separation (MS) increases the risk of occurrence of anxiety, depression, and learning and memory impairment in offspring. However, the underlying molecular biological mechanisms remain unclear. In the current study, offspring CD-1 mice were separated from their mothers from postnatal day 4 to postnatal day 21. At 3 months of age, the male offspring were selected for the evaluation of anxiety- and depression-like behaviors and learning and memory function. Western blotting and RT-PCR were used to examine the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin. Long-term potentiation (LTP) and long-term depression (LTD) were recorded at Schaffer collateral/CA1 synapses. Furthermore, basal synaptic transmission was evaluated via the recording of the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). The results showed that adult offspring CD-1 mice displayed anxiety- and depressive-like behaviors as well as impaired spatial learning and memory abilities. Electrophysiological analysis indicated that MS impaired LTP, enhanced LTD, and reduced the frequency of mEPSCs in pyramidal neurons in the CA1 region. Our findings suggested that MS can lead to anxiety, depression, and cognitive deficits, and these effects are associated with alterations in the levels of synaptic plasticity-associated proteins, consequently, also synaptic plasticity.

Jianghua Kucha black tea containing theacrine attenuates depression-like behavior in CUMS mice by regulating gut microbiota-brain neurochemicals and cytokines

Theacrine and theaflavins are known for their potential to mitigate depression and cognitive impairment. Jianghua Kucha black tea (JH) contains both compounds, yet its antidepressant properties are seldom documented. This study evaluated the effects of JH on depression in chronic unpredictable mild stress (CUMS) mice and explored the underlying mechanisms through integrative analyses of gut microbiota and fecal metabolomics. JH was found to significantly alleviate CUMS-induced depression-like behavior by improving body weight, food intake, 1% sucrose preference, immobility time, and numbers of crossings and standings compared to Zhuyeqi black tea (ZYQ), which contains theaflavins. JH notably altered the gut microbiota composition, enriching genera such as Turicibacter, Faecalibaculum, Akkermansia, and Desulfovibrio, while inhibiting genera norank_f__Muribaculaceae and Lactobacillus. Additionally, JH modified the fecal metabolite profile, characterized by increased levels of several secondary bile acids (BAs) and decreased levels of several purine intermediate metabolites. Furthermore, JH upregulated levels of monoamine neurotransmitters (5-HT and DA) and brain-derived neurotrophic factor (BDNF), while downregulating pro-inflammatory cytokines IL-6 and TNF-α in brain tissue. These findings suggested that JH could mitigate CUMS-induced depression-like behavior, potentially by modulating gut microbiota composition and function, as well as brain neurochemicals and cytokines.

Effects of variation in exercise training load on cognitive performances and neurotrophic biomarkers in patients with coronary artery disease.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. Visit 1 included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o2peak). Visit 2 included cognitive functions assessment. Thirty-nine patients completed the study (LP: n = 20, NLP: n = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: P < 0.001), whereas BDNF concentration increased (time-effect: P < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.18, P = 0.04), and ΔIGF-1 and Δshort-term/working memory (R2 = 0.17, P = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.45, P = 0.02), ΔBDNF and Δshort-term/working memory (R2 = 0.62, P = 0.004), ΔIGF-1 and Δshort-term/working memory (R2 = 0.31, P = 0.01), and ΔIGF-1 and Δexecutive function (R2 = 0.22, P = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD.NEW & NOTEWORTHY We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.

Enhanced phrenic motor neuron BDNF expression elicited by daily acute intermittent hypoxia is undermined in rats with chronic cervical spinal cord injury

Acute intermittent hypoxia (AIH) elicits spinal neuroplasticity and is emerging as a potential therapeutic modality to improve respiratory and non-respiratory motor function in people with chronic incomplete spinal cord injury (SCI). Brain-derived neurotrophic factor (BDNF) is necessary and sufficient for moderate AIH-induced phrenic long-term facilitation, a well-studied form of respiratory motor plasticity. Repetitive daily AIH (dAIH) enhances BDNF expression within the phrenic motor neurons of normal rats, but its effects on BDNF after chronic cervical spinal cord injury (cSCI) are unknown. In contrast to AIH, chronic intermittent hypoxia (CIH), simulating that experienced during sleep apnea, elicits neuropathology and undermines plasticity. Here, we tested the hypothesis that daily AIH vs CIH differentially regulate phrenic motor neuron BDNF expression in spinally intact and injured rats. Rats with and without C2 hemisection (C2Hx; 8 weeks post-injury) were exposed to 28 days of: 1) sham normoxia (Nx, 21% O2); 2) daily AIH (dAIH: 10, 5min of 10.5% O2 per day; 5min normoxic intervals); 3) mild CIH (CIH5/5: 5min of 10.5% O2, 5min intervals, 8 hrs/day); or 4) moderate CIH (CIH2/2: 2min of 10.5% O2, 2min intervals, 8 hrs/day). After 28 days of daily exposure (i.e., 12 weeks post-injury), BDNF immunoreactivity was assessed within phrenic motor neurons identified via retrograde cholera toxin B fragment labeling. In intact rats, daily AIH increased BDNF protein levels in phrenic motor neurons (~31%) but not in rats with C2Hx. CIH had no effects on phrenic motor neuron BDNF levels in intact rats, although there was a trend towards increased phrenic motor neuron BDNF after C2Hx, suggesting the need for further study. Since dAIH effects on phrenic motor neuron BDNF are not observed in rats with chronic cervical SCI, the potential of dAIH to enhance BDNF-dependent phrenic motor plasticity may be suppressed by conditions prevailing with chronic cSCI.

Efficacy of non-invasive brain stimulation for post-stroke sleep disorders: a systematic review and meta-analysis.

This study aimed to systematically assess the clinical efficacy of non-invasive brain stimulation (NIBS) for treating post-stroke sleep disorders (PSSD). We conducted thorough literature search across multiple databases, including PubMed, Web of Science, EmBase, Cochrane Library, Scopus, China Biology Medicine (CBM); China National Knowledge Infrastructure (CNKI); Technology Periodical Database (VIP), and Wanfang Database, focusing on RCTs examining NIBS for PSSD. Meta-analyses were performed using RevMan 5.4 and Stata 14. Eighteen articles were reviewed, including 16 on repetitive Transcranial Magnetic Stimulation (rTMS), one on Theta Burst Stimulation (TBS), and two on transcranial Direct Current Stimulation (tDCS). Meta-analysis results indicated that rTMS within NIBS significantly improved the Pittsburgh Sleep Quality Index (PSQI) score (MD = -1.85, 95% CI [-2.99, -0.71], p < 0.05), the 17-item Hamilton Depression Rating Scale (HAMD-17) score [MD = -2.85, 95% CI (-3.40, -2.30), p < 0.05], and serum brain-derived neurotrophic factor (BDNF) levels [MD = 4.19, 95% CI (2.70, 5.69), p < 0.05], while reducing the incidence of adverse reactions [RR = 0.36, 95% CI (0.23, 0.55), p < 0.05]. TBS significantly improved the PSQI score in patients with PSSD (p < 0.05). Conversely, tDCS significantly improved the HAMD-17 score in PSSD patients [MD = -1.52, 95% CI (-3.41, -0.64), p < 0.05]. Additionally, rTMS improved sleep parameters, including Stage 2 sleep (S2%) and combined Stage 3 and 4 sleep (S3 + S4%) (p < 0.05), while tDCS improved total sleep time (TST) and sleep efficiency (SE) (p < 0.05).Subgroup analysis results indicated: (1) Both LF-rTMS and HF-rTMS improved PSQI scores (p < 0.05). (2) Both rTMS combined with medication and rTMS alone improved PSQI scores (p < 0.05). Compared to the sham/blank group, the rTMS group showed improvements in SE, sleep latency (SL), S1%, S3 + S4%, and REM sleep (REM%). The rTMS combined with medication group showed improved SL compared to the medication-only group (p < 0.05). NIBS effectively improves sleep quality, structure, depression levels, and BDNF levels in PSSD patients, while also being safe. Further investigations into the potential of NIBS in PSSD treatment may provide valuable insights for clinical applications. https://www.crd.york.ac.uk/prospero/, CRD42023485317.

Regenerative potentials of bone marrow mesenchymal stem cells derived exosomes or its combination with zinc in recovery of degenerated circumvallate papilla following surgical bilateral transection of glossopharyngeal nerve in rats

BackgroundTaste buds’ innervation is necessary to sustain their cell turnover, differentiated taste buds and nerve fibers in circumvallate papilla (CVP) disappear following glossopharyngeal nerve transection. Normally, taste buds recover to baseline number in about 70 days. Bone marrow stem cell (BM-MSC) derived exosomes or their combination with Zinc chloride are used to assess their potential to speed up the regeneration process of CVP following bilateral deafferentation.MethodsTwenty-eight male Sprague-Dawley rats were randomly divided into four groups; Group I: subjected to sham operation followed by IP injection of saline. The other experimental groups (II, III and IV) were subjected to surgical bilateral transection of glossopharyngeal nerve. Group II received single IP injection of saline. Group III received single IV injection of BM-MSC-derived exosomes (100 µg). Group IV received single IV injection of BM-MSC-derived exosomes and single IP injection of zinc chloride (5 mg/kg). After 28 days, CVP was dissected and prepared for histological and histomorphometric analysis, RT-PCR for cytokeratin 8 gene expression, ELISA to assess protein level of brain-derived neurotrophic factor, redox state analysis of malondialdehyde and glutathione content, followed by statistical analysis.ResultsHistopathologically, group II exhibited great tissue damage with marked reduction in taste buds and signs of degeneration in the remaining ones. Group III was close to control group with marked improvement in taste buds’ number and structure. Group IV showed inferior results when compared to group III, with many immature taste buds and signs of degeneration. Statistical results showed that groups I and III have significantly higher values than groups II and IV regarding taste buds’ number, cytokeratin 8, and reduced glutathione. However, malondialdehyde demonstrated high significant values in group IV compared to groups I and III. Regarding brain-derived neurotrophic factor, group III had significantly higher values than group II.ConclusionBM-MSC-derived exosomes have superior regenerative potentials in acceleration of CVP and nerve healing following bilateral transection of glossopharyngeal nerve in contrary to its combination with zinc chloride.Graphical

Plasma Brain-Derived Neurotrophic Factor (BDNF) Levels and BDNF Promoters’ DNA Methylation in Workers Exposed to Occupational Stress and Suffering from Psychiatric Disorders

Introduction: Decreased plasma BDNF (pBDNF) levels have been proposed as a biomarker in the illness phases of mood disorders. This cross-sectional study aimed to evaluate the pBDNF and BDNF promoters’ DNA methylation levels in workers exposed to occupational stress and suffering from work-related stress disorders. Methods: the pBDNF and BDNF exon I and IV promoters’ methylation levels were measured by specific immunoassays and methylation-sensitive high-resolution melting (MS-HRM) in 62 patients with adjustment disorders (AD), 79 patients with major depressive disorder (MDD) and 44 healthy controls. Occupational stress was evaluated in the patients and controls using the Job Content Questionnaire (JCQ). Results: the pBDNF levels were significantly higher in the MDD (p &lt; 0.001) and AD (p &lt; 0.0001) patients than in the controls. The MDD patients showed significantly lower pBDNF levels than the AD ones (p = 0.01). The BDNF exon I and IV promoters’ methylation levels were significantly higher in the MDD patients than in the AD ones (exon I promoter: p = 0.0001, exon IV promoter: p &lt; 0.0001) and controls (exon I promoter: p = 0.0001, exon IV promoter: p &lt; 0.0001). In the patients, but not in the controls, the BDNF promoters’ methylation levels showed significant negative correlations with occupational stress. Conclusions: BDNF could play a key role in the pathophysiology of stress-related disorders and the peripheral elevation of it observed in patients exposed to occupational stress could suggest a protective mechanism for neurons from stress-mediated damage. The elevation of the pBDNF levels, even in MDD, may characterize a “reactive” subtype of depressive episode, while the significant elevation of the BDNF promoters’ methylation levels in depressed patients could indicate a predisposition to more severe illness under stress. Further research is needed, focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases.

Fluoxetine Ameliorates Cognitive Deficits in High-Fat Diet Mice by Regulating BDNF Expression.

High-fat diet (HFD) induced obesity is associated with depression-related behavioral and neurogenic changes and may lead to cognitive impairment. Fluoxetine (FXT), the most commonly used antidepressant, may alleviate depressive symptoms by increasing neurogenesis, but the potential efficacy of FXT for HFD-induced cognitive deficits is unclear. In this study, we established an obese HFD mouse model by feeding three-week-old male C57BL/6N mice with a chronic HFD for 18 weeks, then assessed adipose tissue morphology by magnetic resonance imaging and histopathology, assessed cognitive function by Morris water maze and novel object recognition tests, and detected DCX+ and BrdU+ expression in the hippocampal dentate gyrus (DG) region by immunofluorescence bioassay. Western blot detected brain-derived neurotrophic factor (BDNF) levels and CREB-BDNF pathway-related genes were assayed by Quantitative RT-PCR. The results of the study showed that HFD contributes to obesity and cognitive deficits, and more importantly, it also reduces BDNF expression and neurogenesis levels in the hippocampus. Subsequently, we found that treatment with FXT (10 mg/kg/day) ameliorated chronic HFD-induced cognitive deficits and increased the expression of Nestin, BrdU+, and DCX+ in the DG, restored BDNF expression in the hippocampus and increased the expression of genes related to CREB, BDNF, NGF, and MAPK1. In conclusion, our data elucidated that FXT ameliorates cognitive deficits and reduces chronic HFD-induced neurogenesis by restoring BDNF expression and CREB-BDNF signaling, this provides a good basis and scientific significance for future research on the clinical treatment of obesity.

Corticosterone-Mediated BDNF Changes and Their Effects on Adult Neurogenesis in Depression

Adult neurogenesis, the process of generating functional neurons from neural precursor cells in the adult brain, is essential for cognitive function and emotional regulation. Major Depressive Disorder (MDD), characterized by persistent sadness and decreased psychosocial function, is associated with impaired adult hippocampal neurogenesis (AHN). Elevated levels of corticosterone (CORT), a glucocorticoid released in response to stress, have been shown to downregulate brain-derived neurotrophic factor (BDNF), a crucial regulator of neurogenesis, thereby inhibiting AHN. Despite significant advances in understanding the impact of CORT and BDNF on neurogenesis, the precise molecular and cellular pathways involved remain unclear. This review highlights key gaps in the research, particularly the need for a deeper understanding of how glucocorticoid and mineralocorticoid receptors regulate BDNF transcription, the role of autophagic pathways in BDNF degradation, and the influence of glutamatergic signaling on these processes. Future research should focus on elucidating these mechanisms to develop targeted therapeutic strategies, including pharmacological interventions that modulate BDNF and CORT levels and lifestyle modifications like exercise and adequate sleep to enhance neurogenesis. Understanding these complex interactions will be crucial for advancing treatments for depression and improving mental health outcomes.