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The prevalence of Alzheimer's disease (AD) is on the rise globally, and everyone who develops AD eventually experiences mild cognitive impairment (MCI) first. Timely intervention at an early stage of the disease may mitigate disease progression. Recent studies indicate that BDNF and MMP-9 play a significant role in the pathogenesis of AD. Therefore, this study aims to ascertain whether there are differences in plasma BDNF and MMP-9 levels between individuals with mild cognitive impairment due to AD and those with normal cognition, and to analyze the factors influencing mild cognitive impairment.This case-control study included 102 individuals with mild cognitive impairment and 102 controls, matched by age and sex. Participants completed a series of questionnaires, neuropsychological assessments, and clinical examinations. Plasma concentrations of BDNF and MMP-9 of the participants were quantified using ELISA. Subsequently, the factors influencing MCI were analyzed using univariate and multivariate logistic regression. The differences in plasma BDNF levels, MOCA total scores, and scores in various cognitive domains (including visuospatial and executive abilities, abstract thinking, attention, language, naming, and delayed memory) between the MCI and the control groups showed statistically significant (p < 0.05). Logistic regression analysis revealed that plasma BDNF levels and years of formal education were significantly negatively associated with MCI. This study indicates that plasma BDNF and years of formal education are protective factors influencing cognitive function. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that may develop after experiencing traumatic events. Preclinical studies use various methods to induce PTSD-like models such as fear-conditioning, single-prolonged stress (SPS), restraint stress, and social defeat. Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophin in mood regulation. Evidence shows BDNF changes in different neuropsychiatric disorders particularly PTSD. This review examined BDNF alterations in preclinical rodent models of PTSD where we demonstrated a wide range of paradoxical changes in BDNF. We found that the fear-conditioning model produced the most inconsistent alterations in BDNF, and suggest that conclusions drawn from these changes be approached with caution. We suggest that BDNF maladaptive changes in social defeat and restraint stress models may be related to the duration of stress, while the SPS model appears to have more consistent results. Ultimately, we propose that evaluating BDNF alterations in the process of treating PTSD symptoms may not be a reliable factor. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is usually associated with cognitive impairment, neuropathic pain, and reduced brain‐derived neurotrophic factor (BDNF) levels. BDNF via tropomyosin receptor kinase B (TrkB) exerts neuroprotection by activating protein kinase B (Akt) to inhibit glycogen synthase kinase‐3β (GSK3β). Although Vitamin D3 (VitD3) has demonstrated favorable metabolic and neuronal outcomes in MetS, the precise molecular mechanisms underlying its neuroprotective effects remain poorly elucidated. We aimed to test the hypothesis that VitD3 mitigates MetS‐induced cognition deficits and neuropathic pain via modulating the BDNF/TRKB/Akt/GS3Kβ signaling pathway. MetS was induced in male rats by 10% fructose‐supplemented water and 3% salt‐enriched diet. After 6 weeks, normal and MetS rats received either vehicle or VitD3 (10 µg/kg/day) for an additional 6 weeks. Glycemic status, lipid profile, and behavioral changes were assessed. The advanced glycation end products (AGEs), and markers of inflammation (TNF‐α and NF‐κB), oxidative stress (malondialdehyde), and apoptosis (caspase3), as well as BDNF, TrkB, PI3K, Akt, GSK3β, phosphorylated tau, and amyloid beta (Aβ) were assessed in the cerebral cortex. MetS rats had deteriorated glycemic and lipid profiles, higher AGEs, reduced levels of BDNF, TrkB, PI3K, and active Akt, along with increased GSK3β levels, inflammation, oxidative stress, and apoptosis. These changes were associated with higher levels of cognitive impairment markers phosphorylated tau and Aβ, as well as behavioral changes indicative of cognitive impairment and neuropathic pain. VitD3 improved the cognitive and behavioral alterations, while mitigating the associated molecular derangements. Our results indicate that VitD3 may exert neuroprotective effects by modulating the BDNF/TrkB/PI3K/Akt/GSK3β signaling pathway. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Asiaticoside, the main active ingredient of Centella asiatica, is a pentacyclic triterpenoid compound. Previous studies have suggested that asiaticoside possesses neuroprotective and anti-depressive properties, however, the mechanism of its anti-depressant action not fully understood. In recent years, a growing body of research on anti-depressants has focused on the microbiota-gut-brain axis, we noted that disruption of the gut microbial community structure and diversity can induce or exacerbate depression, which plays a key role in the regulation of depression. Methods: Behavioral experiments were conducted to detect depression-like behavior in mice through sucrose preference, forced swimming, and open field tests. Additionally, gut microbial composition and short-chain fatty acid (SCFA) levels in mouse feces were analyzed 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5-HT1A) expression in mice was assessed by western blotting. Changes in serum levels of inflammatory factors, neurotransmitters, and hormones were measured in mice using ELISA. Results: This study revealed that oral administration of asiaticoside significantly improved depression-like behavior in chronic unpredictable mild stress (CUMS) mice. It partially restored the gut microbial community structure in CUMS mice, altered SCFA metabolism, regulated the hypothalamic-pituitary-adrenal axis (HPA axis) and inflammatory factor levels, upregulated BDNF and 5-HT1A receptor protein expression, and increased serum serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal that asiaticoside exerts antidepressant effects via the microbiota-gut-brain axis. Conclusions: These results suggested that asiaticoside exerts antidepressant effects through the microbiota-gut-brain axis in a CUMS mouse model. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is essential for the development and functioning of the vestibular system. BDNF promotes the growth, differentiation, and synaptic plasticity of vestibular neurons, ensuring their normal operation and maintenance. According to research, BDNF is pivotal during vestibular compensation, aiding in the recovery of neuron function by remodeling the spontaneous resting potentials of damaged vestibular neurons. Additionally, BDNF exhibits dose-dependent and age-dependent characteristics during vestibular system development, with its deficiencies leading to the degeneration of vestibular neurons. BDNF dynamically interacts with other neurotrophic factors, such as fibroblast growth factor-2 (FGF-2) and glial cell line-derived neurotrophic factor (GDNF), synergistically enhancing neuron survival and functionality. This review outline the function of BDNF in the vestibulocochlear system and explores its potential therapeutic applications, offering fresh perspectives and guidance for future research and treatment of vestibulocochlear system disorders. [ABSTRACT FROM AUTHOR]

Background and Aim: The prevalence of overweight and obesity is increasing dramatically due to unhealthy lifestyles. This study aimed to determine the effects of six weeks of total-body resistance exercise (TRX) combined with purslane supplementation on serum levels of brain-derived neurotrophic factor (BDNF), adropin, and nesfatin in overweight girls. Methods: In this semi-experimental study, 32 overweight female students aged 16 to 18 years (BMI > 25) from Ganaveh County, Bushehr Province, Iran, were randomly selected. The participants were divided into four groups: exercise, supplement, exercise + supplement, and placebo. The exercise groups performed TRX exercises consisting of 9 to 11 movements for six weeks, with three sessions per week, each lasting 60 minutes. Purslane supplementation was administered as two 500 mg capsules of purslane (Perpin Ala) taken daily after breakfast and lunch. Serum levels of BDNF, adropin, and nesfatin were measured using ELISA at the beginning and end of the six-week study. Results: The serum levels of BDNF in the exercise + supplement group showed significant differences compared to the exercise, supplement, and control groups (P < 0.05). Additionally, the serum levels of nesfatin were significantly different between the exercise + supplement group and the control group (P < 0.05). However, there were no significant differences in serum levels of adropin among the groups (P > 0.05). Conclusion: The findings suggest that a combination of TRX exercises and purslane supplementation over six weeks positively affects BDNF and nesfatin levels in young girls, potentially aiding in weight reduction. Further research is needed to explore this area more comprehensively.

Background: Impulsivity assessment may serve as a valuable clinical tool in the stratification of suicide risk. Acting without forethought is a crucial feature in the psychopathology of many psychiatric disturbances and corresponds with suicidal ideations, behaviors, and attempts. Methods: We present data on biological and psychological correlates of impulsivity among young adults (n = 47). Psychological analysis included both the self-description questionnaire—Barratt Impulsiveness Scale (BIS-11)—and neuropsychological behavioral tests, including the Iowa Gambling Task (IGT), the Simple Response Time task (SRT), and the Continuous Performance Test (CPT). mRNA and micro-RNA were isolated from peripheral blood mononuclear cells (PBMC). Expression levels of Brain-Derived Neurotrophic Factor (BDNF) mRNA and its regulatory micro RNAs, mir-1-3p, mir-15a-5p, mir-26a-5p, mir-26b-5p, and mir-195-5p, were analyzed using the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. proBDNF and BDNF plasma protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Significant correlations between BDNF mRNA and mir-15a-5p as well as proBDNF levels and mir-1-3p were detected. proBDNF protein levels correlated with motor and perseverance, while mir-26b correlated with cognitive complexity subdimensions of the BIS-11 scale. Correlations between BDNF, miRNAs, and the results of neuropsychological tests were also detected. Conclusions: The BDNF pathway shows a clinical potential in searching for biomarkers of impulse-control impairment. BDNF-regulatory micro-RNAs are detectable and related to clinical parameters in the studied population, which needs further research. [ABSTRACT FROM AUTHOR]

Recently, number of adolescent and advanced age pregnancies increased and became an important social issue. There are conflicting results on maternal and perinatal outcomes of those pregnancies. Maternal anemia is one of the factors affecting the newborn central nervous system. It is known that BDNF is at low levels during fetal development and increases after birth, while NGF regulates the life and development of dorsal root ganglion and sympathetic cells in embryonic and postnatal life. In this study, the effect of maternal anemia on placental brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in young and older pregnancies was examined. The study group consists of anemic pregnant women under 18 years of age and over 35 years of age, and the control group consists of non-anemic pregnant women under 18 years of age and over 35 years of age (n:30, n:36, n:30, n:39, respectively). In BDNF immunostaining, a weak-moderate reaction was observed in the anemic and non-anemic groups under 18 years of age, a weak-moderate reaction in the anemic group over 35 years of age, and a strong reaction in the non-anemic group over 35 years of age. In NGF immunostaining, a weak reaction was observed in the anemic group under the age of 18, a strong immune reaction in the non-anemic group under the age of 18, a moderate-strong reaction in the anemic group over the age of 35, and a very strong reaction in the non-anemic group over the age of 35. While the BDNF reaction was higher in anemic pregnant women under the age of 18, the NGF reaction was found to be lower. While neurotrophins (BDNF and NGF) are higher in older age pregnant women without anemia, they are lower in older anemic pregnant women. It has been determined that anemia suppresses neurotrophins in the placenta in older age groups. [ABSTRACT FROM AUTHOR]

Early developmental malnutrition exerts adverse effects on the structural, neurochemical, and neurophysiological maturation of cerebral cells by disrupting the process of neurogenesis. Pasak bumi (Eurycoma longifolia Jack) and seluang fish (Rasbora spp.), two indigenous natural resources of South Kalimantan, Indonesia, are believed to harbor nutritional components capable of mitigating these deleterious effects. We aimed to assess the impact of administering pasak bumi, seluang fish, and pure docosahexaenoic acid (DHA) on the neurogenesis process in malnourished rat models. The Rattus norvegicus specimens were partitioned into seven distinct cohorts, each consisting of five rats: healthy rats in the negative control group (KN), while malnourished rats in the positive control (KP) and treatment groups (P1, P2, P3, P4, and P5). Both the KP and KN groups received a placebo and a standard feed. The treatment groups received different interventions for five weeks: standard feed alongside pasak bumi extract for the P1 group, standard feed and DHA for the P2 group, standard feed in combination with pasak bumi extract and DHA for the P3 group, seluang fish for the P4 group, and pasak bumi extract and seluang fish for the P5 group. The doses determined for the pasak bumi extract and DHA were 15 and 1 mg/kg bw, respectively. The parameters evaluated consisted of the levels of brain-derived neurotrophic factor (BDNF), neural progenitor cell β-tubulin 3 (Tuj-1) expression, and peroxisome proliferator-activated receptor gamma (PPARγ). The data were subjected to analysis through the Kruskal-Wallis test and analysis of variance (ANOVA) at a 95% confidence level. A value of p<0.05 was considered significant. Statistically significant differences were observed in the BDNF levels (p=0.00) and Tuj-1 expressions (p=0.01) across all groups. In conclusion, the combined administration of pasak bumi and seluang fish demonstrates the capacity of enhancing neurogenesis in malnourished rats, as evidenced by elevated BDNF levels and Tuj-1 expressions. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive–compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin. [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]

Neurotrophic factors play pivotal roles in shaping brain development and function, with brain-derived neurotrophic factor (BDNF) emerging as a key regulator in various physiological processes. This review explores the intricate relationship between BDNF and anorexia nervosa (AN), a complex psychiatric disorder characterized by disordered eating behaviors and severe medical consequences. Beginning with an overview of BDNF's fundamental functions in neurodevelopment and synaptic plasticity, the review delves into recent clinical and preclinical evidence implicating BDNF in the pathophysiology of AN. Specifically, it examines the impact of BDNF polymorphisms, such as the Val66Met variant, on AN susceptibility, prognosis, and treatment response. Furthermore, the review discusses the interplay between BDNF and stress-related mood disorders, shedding light on the mechanisms underlying AN vulnerability to stress events. Additionally, it explores the involvement of BDNF in metabolic regulation, highlighting its potential implications for understanding the metabolic disturbances observed in AN. Through a comprehensive analysis of clinical data and animal studies, the review elucidates the nuanced role of BDNF in AN etiology and prognosis, emphasizing its potential as a diagnostic and prognostic biomarker. Finally, the review discusses limitations and future directions in BDNF research, underscoring the need for further investigations to elucidate the complex interplay between BDNF signaling and AN pathology. [ABSTRACT FROM AUTHOR]

Neurotrophins are important regulators of neuronal and non-neuronal functions. As such, the neurotrophins and their receptors, the tropomyosin receptor kinase (Trk) family of receptor tyrosine kinases, has attracted intense research interest and their role in multiple diseases including Alzheimer's disease has been described. Attempts to administer neurotrophins to patients have been reported, but the clinical trials have so far have been hampered by side effects or a lack of clear efficacy. Thus, much of the focus during recent years has been on identifying small molecules acting as agonists or positive allosteric modulators (PAMs) of Trk receptors. Two examples of successful discovery and development of PAMs are the TrkA-PAM E2511 and the pan-Trk PAM ACD856. E2511 has been reported to have disease-modifying effects in preclinical models, whereas ACD856 demonstrates both a symptomatic and a disease-modifying effect in preclinical models. Both molecules have reached the stage of clinical development and were reported to be safe and well tolerated in clinical phase 1 studies, albeit with different pharmacokinetic profiles. These two emerging small molecules are interesting examples of possible novel symptomatic and disease-modifying treatments that could complement the existing anti-amyloid monoclonal antibodies for the treatment of Alzheimer's disease. This review aims to present the concept of positive allosteric modulators of the Trk receptors as a novel future treatment option for Alzheimer's disease and other neurodegenerative and cognitive disorders, and the current preclinical and clinical data supporting this new concept. Preclinical data indicate dual mechanisms, not only as cognitive enhancers, but also a tentative neurorestorative function. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies). [ABSTRACT FROM AUTHOR]

Background: Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors in rodents. On the other hand, lithium, as one of the oldest drugs used in neuropsychiatric disorders, is still one of the best drugs for the treatment and control of bipolar disorder. In this study, we aimed to investigate the role of chronic short-term REM SD in the induction of manic-like behaviors in female rats. Methods: The rats were exposed to REM SD for 14 days (6 hours/day). Lithium was intraperitoneally injected at the doses of 10, 50, and 100 mg/kg. Results: REM SD induced hyperactivity and OCD-like behavior, and decreased anxiety, depressive-like behavior, and pain subthreshold. REM SD also impaired passive avoidance memory and decreased hippocampal brain-derived neurotrophic factor (BDNF) expression level. Lithium at the doses of 50 and 100 mg/kg partly and completely abolished these effects, respectively. However, lithium (100 mg/kg) increased BDNF expression level in control and sham REM SD rats with no significant changes in behavior. Conclusions: Chronic short-term REM SD may induce a mania-like model and lead to OCD-like behavior and irritability. In the present study, we demonstrated a putative rodent model of mania induced by chronic REM SD in female rats. We suggest that future studies should examine behavioral and mood changes following chronic REM SD in both sexes. Furthermore, the relationship between manic-like behaviors and chronic REM SD should be investigated. [ABSTRACT FROM AUTHOR]

Omega-3 fatty acids (omega-3 FAs) have attracted the attention of researchers because of their influence on circulatory levels of brain-derived neurotrophic factor (BDNF). Our objective was to review systematically and Meta-analyze randomized controlled trials (RCTs) to assess the effects of omega-3 FAs supplementation on serum BDNF concentration. Scopus, PubMed, Web of Science, and Cochrane Library were systematically searched until April 2023. The Cochrane risk of bias assessment tool was utilized to evaluate the quality of the studies. A random-effects model was employed to estimate the overall effect size of BDNF levels, using the Standard Mean Difference (SMD) and a 95% confidence interval (CI). The heterogeneity among the studies was assessed using chi-squared and I2 statistics. A total of 12 studies involving 587 subjects were included. The supplementation of PUFA was found to be associated with a significant increase in serum levels of BNDF in the group receiving the supplements, as compared to the placebo group (SMD: 0.72 pg/mL, 95% CI: 0.28, 1.15; P < 0.001) (I2 = 84.39%, P < 0.001). Sub-group analyses revealed similar findings in trials with fewer than 10 weeks, which utilized both animal (fish oil) and herbal (flaxseed) forms of omega-3 supplements with a high daily dosage of 2000mg. The present systematic review and meta-analysis indicate the efficacy of omega-3 FAs in increasing the serum concentration of BDNF. Therefore, omega-3 FAs should be prioritized as agents for increasing BDNF in interventions. [ABSTRACT FROM AUTHOR]

Background and Purpose: In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment and predicting the treatment response. Currently, tRNA‐derived small ribonucleic acids (tsRNAs) have been established as promising non‐invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development. Experimental Approach: Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA‐Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real‐time polymerase chain reaction (qRT‐PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment were analysed. Key Results: In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 up‐regulated and 4 down‐regulated). qRT‐PCR was used to validate the expression of six tsRNAs that were up‐regulated in MDD (tiRNA‐1:20‐chrM.Ser‐GCT, tiRNA‐1:33‐Gly‐GCC‐1, tRF‐1:22‐chrM.Ser‐GCT, tRF‐1:31‐Ala‐AGC‐4‐M6, tRF‐1:31‐Pro‐TGG‐2 and tRF‐1:32‐chrM.Gln‐TTG). Interestingly, serum tiRNA‐Gly‐GCC‐001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA‐Gly‐GCC‐001 is predicted to suppress brain‐derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA‐Gly‐GCC‐001 down‐regulation was evident following an 8‐week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy. Conclusion and Implications: Our current work reports for the first time that tiRNA‐Gly‐GCC‐001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that causes physical damage to neuronal connections, leading to brain atrophy. This disruption of synaptic connections results in mild to severe cognitive impairments. Unfortunately, no effective treatment is currently known to prevent or reverse the symptoms of AD. The aim of this study was to investigate the effects of three synthetic peptides, i.e., KLVFF, RGKLVFFGR and RIIGL, on an AD in vitro model represented by differentiated SH-SY5Y neuroblastoma cells exposed to retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). The results demonstrated that RIIGL peptide had the least significant cytotoxic activity to normal SH-SY5Y while exerting high cytotoxicity against the differentiated cells. The mechanism of RIIGL peptide in the differentiated SH-SY5Y was investigated based on changes in secretory proteins compared to another two peptides. A total of 380 proteins were identified, and five of them were significantly detected after treatment with RIIGL peptide. These secretory proteins were found to be related to microtubule-associated protein tau (MAPT) and amyloid-beta precursor protein (APP). RIIGL peptide acts on differentiated SH-SY5Y by regulating amyloid-beta formation, neuron apoptotic process, ceramide catabolic process, and oxidative phosphorylation and thus has the potentials to treat AD. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) plays a vital role in supporting neuronal survival, differentiation, and promoting synaptogenesis, thereby facilitating synaptic plasticity in the central nervous system. Administration of exogenous BDNF is a crucial approach for treating central nervous system injuries. However, the inability of sustained drug release to match disease activity often leads to insufficient drug accumulation in the injured area (ineffectiveness) and severe side effects induced by the drug (toxicity). Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are typically upregulated after tissue damage, and their upregulated expression levels represent the degree of disease activity. In this study, we utilized bioengineering techniques to prepare a BDNF that can specifically bind to collagen and be released in response to MMP substrate cleavage (collagen binding domain tissue inhibitor of matrix metalloproteinases brain-derived neurotrophic factor, CBD-TIMP-BDNF). We verified the ability of CBD-BDNF and CBD-TIMP-BDNF to specifically bind to collagen through collagen binding experiments, examined the characteristics of CBD-TIMP-BDNF in response to MMP-2 to release BDNF, and detected the biological activities of both recombinant proteins. The results demonstrated that the established microenvironment-controlled BDNF release system can respond to MMP-2 to release BDNF. The recombinant proteins CBD-BDNF and CBD-TIMP-BDNF exhibited similar biological activities to the BDNF standard. Targeting the upregulated expression of MMPs after spinal cord injury as a trigger for drug release, it is expected to achieve on-demand release of BDNF in response to the severity of the disease. [ABSTRACT FROM AUTHOR]

The brain-derived neurotrophic factor (BDNF) plays a crucial role during neuronal development as well as during differentiation and synaptogenesis. They are important proteins present in the brain that support neuronal health and protect the neurons from detrimental signals. The results from the present study suggest BDNF expression can be increase up to ~8-fold by treating the neuroblastoma cells SHSY-5Y with an herbal extract of Oroxylum indicum (50 μg/mL) and ~5.5-fold under lipopolysaccharides (LPS)-induced inflammation conditions. The Oroxylum indicum extract (Sabroxy) was standardized to 10% oroxylin A, 6% chrysin, and 15% baicalein. In addition, Sabroxy has shown to possess antioxidant activity that could decrease the damage caused by the exacerbation of radicals during neurodegeneration. A mode of action of over expression of BDNF with and without inflammation is proposed for the Oroxylum indicum extract, where the three major hydroxyflavones exert their effects through additive or synergistic effects via five possible targets including GABA, Adenoside A2A and estrogen receptor bindings, anti-inflammatory effects, and reduced mitochondrial ROS production. [ABSTRACT FROM AUTHOR]

Seizure is known to induce oxidative stress which may initiate neuronal death. Oxidant-antioxidant imbalance often leads to mitochondrial dysfunction, inflammation, and apoptosis in the brain which may further result in the development of seizure. Phenolic compounds such as curcumin and rosmarinic acid are reported to control convulsions and seizures in pentylenetetrazol induced seizures models by suppressing seizure time, oxidative stress and inflammation indirectly. Sinapic acid (SA), a polyphenolic product of hydroxycinnamic acid found in various plants, exhibits anti-inflammatory, antioxidant and anxiolytic effects. In this study, we investigated the effects of sinapic acid on pentylenetetrazol induced seizures in rats through oxidative stress, inflammation, apoptosis, and neurotrophic factor. A total of 28 male Wistar Albino rats weighing 200-220 g were divided into four equal groups (n=7/group). The treatment groups received 10 mg/kg and 20 mg/kg SA, respectively, by oral gavage for five consecutive days along with pentylenetetrazol (45 mg/kg, intraperitoneal) to induce seizures. The levels of Total oxidant status (TOS), Total antioxidant status (TAS), TNF-α, IL-1β, and Brain-derived neurotrophic factor (BDNF) were measured in the cortex and hippocampus. Additionally, caspase 3 and caspase 9 levels, as well as the immunoreactivity of Cleaved caspase 3, were determined in the hippocampus. The results showed that pretreatment with 20 mg/kg SA delayed the latency of generalized tonic-clonic seizures (GTCS) and first myoclonic jerk, reduced GTCS duration, and improved seizure score and cognitive function. Importantly, the 20 mg/kg SA pretreatment resulted in decreased levels of TOS, TNF-α, IL-1β, and BDNF in the cortex and hippocampus, while increasing TAS levels in these brain areas. Moreover, the 20 mg/kg SA reduced hippocampal caspase 3 and caspase 9 levels, as well as the immunoreactivity of Cleaved caspase 3 in rats with pentylenetetrazol-induced seizures. These findings suggest that the anti-seizure effects of SA are mediated by BDNF modulation, as well as its anti-oxidant, anti-inflammatory, and antiapoptotic properties. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to investigate regenerative process by immunohistochemical analysis and evaluate periodontal tissue regeneration following a topical application of BDNF to inflamed 3‐wall intra‐bony defects. Background: Brain‐derived neurotrophic factor (BDNF) plays a role in the survival and differentiation of central and peripheral neurons. BDNF can regulate the functions of non‐neural cells, osteoblasts, periodontal ligament cells, endothelial cells, as well as neural cells. Our previous study showed that a topical application of BDNF enhances periodontal tissue regeneration in experimental periodontal defects of dog and that BDNF stimulates the expression of bone (cementum)‐related proteins and proliferation of human periodontal ligament cells. Methods: Six weeks after extraction of mandibular first and third premolars, 3‐wall intra‐bony defects were created in mandibular second and fourth premolars of beagle dogs. Impression material was placed in all of the artificial defects to induce inflammation. Two weeks after the first operation, BDNF (25 and 50 μg/mL) immersed into atelocollagen sponge was applied to the defects. As a control, only atelocollagen sponge immersed in saline was applied. Two and four weeks after the BDNF application, morphometric analysis was performed. Localizations of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA)‐positive cells were evaluated by immunohistochemical analysis. Results: Two weeks after application of BDNF, periodontal tissue was partially regenerated. Immunohistochemical analyses revealed that cells on the denuded root surface were positive with OPN and PCNA. PCNA‐positive cells were also detected in the soft connective tissue of regenerating periodontal tissue. Four weeks after application of BDNF, the periodontal defects were regenerated with cementum, periodontal ligament, and alveolar bone. Along the root surface, abundant OPN‐positive cells were observed. Morphometric analyses revealed that percentage of new cementum length and percentage of new bone area of experimental groups were higher than control group and dose‐dependently increased. Conclusion: These findings suggest that BDNF could induce cementum regeneration in early regenerative phase by stimulating proliferation of periodontal ligament cells and differentiation into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration in inflamed 3‐wall intra‐bony defects. [ABSTRACT FROM AUTHOR]

Social isolation is a reliable method used for the induction of depression and psychiatric disorders in rodents. It has been suggested that social isolation can lead to hyperlocomotion, as a schizophrenic-like symptom in rodents. On the other hand, crocin (the major constituent of Crocus sativus) induces a wide-range of neuroprotective and mood enhancer effects. In the present study, we aimed to investigate the effect of acute crocin on social isolation-induced behavioral changes and BDNF expression in the hippocampus. Novelty-suppressed feeding test, open field test, marble burying test, hot plate, forced swim test, and the shuttle box were used to assess anxiety-like behavior, locomotor activity, obsessive–compulsive-like (OCD-like) behavior, pain threshold, depressive-like behavior, and passive avoidance memory, respectively. Real-time PCR was used to assess BDNF hippocampal expression level. The results showed that social isolation decreased anxiety- and depressive-like behavior, pain threshold, and BDNF expression, and induced OCD-like behavior and hyperlocomotion. Crocin dose-dependently restored the effect of social isolation on pain threshold, locomotor activity, depressive-like behavior, OCD-like behavior, and BDNF expression. Passive avoidance memory performance was also unaffected. In conclusion, we showed a hyperlocomotion profile and OCD-like behaviors, and a robust decrease in pain threshold in socially isolated rats. It can be suggested that social isolation from adolescence induces a "hyperlocomotion state" that affects all the behavioral functions of rats. Also, the function of BDNF can be related to a hyperlocomotion state and OCD-like symptom. It seems that BDNF expression level can be related to the therapeutic effect of crocin. [ABSTRACT FROM AUTHOR]

Brain‐derived neurotrophic factor (Bdnf) plays a critical role in brain development, dendritic growth, synaptic plasticity, as well as learning and memory. The rodent Bdnf gene contains nine 5′ non‐coding exons (I–IXa), which are spliced to a common 3′ coding exon (IX). Transcription of individual Bdnf variants, which all encode the same BDNF protein, is initiated at unique promoters upstream of each non‐coding exon, enabling precise spatiotemporal and activity‐dependent regulation of Bdnf expression. Although prior evidence suggests that Bdnf transcripts containing exon I (Bdnf I) or exon IV (Bdnf IV) are uniquely regulated by neuronal activity, the functional significance of different Bdnf transcript variants remains unclear. To investigate functional roles of activity‐dependent Bdnf I and IV transcripts, we used a CRISPR activation system in which catalytically dead Cas9 fused to a transcriptional activator (VPR) is targeted to individual Bdnf promoters with single guide RNAs, resulting in transcript‐specific Bdnf upregulation. Bdnf I upregulation is associated with gene expression changes linked to dendritic growth, while Bdnf IV upregulation is associated with genes that regulate protein catabolism. Upregulation of Bdnf I, but not Bdnf IV, increased mushroom spine density, volume, length, and head diameter, and also produced more complex dendritic arbors in cultured rat hippocampal neurons. In contrast, upregulation of Bdnf IV, but not Bdnf I, in the rat hippocampus attenuated contextual fear expression. Our data suggest that while Bdnf I and IV are both activity‐dependent, BDNF produced from these promoters may serve unique cellular, synaptic, and behavioral functions. [ABSTRACT FROM AUTHOR]

This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (−0.309; −0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the onset of symptoms, typically occurring later in life, and significant deficits in cognitive functions including learning, memory, speech, and behavior. Ongoing research endeavors seek to explore methods for preventing and treating AD, as well as delving into the molecular mechanisms underlying existing and novel therapeutic approaches encompassing exercise, diet, and drug regimens for individuals with AD or those at risk of developing AD. Among these interventions, dietary interventions have garnered increasing attention due to their potential in addressing the disease. Eating is among the most fundamental of human daily activities, and controlled dietary practices, such as fasting, have gained prominence as essential clinical methods for disease prevention and treatment. Research findings indicate that fasting holds promise in effectively alleviating and improving the cognitive decline associated with age or as consequence of disease. The clinical efficacy of fasting in addressing AD and related disorders might be grounded in its influence on various molecular mechanisms, including neuroinflammation, glial cell activation, insulin resistance, autophagy regulation, nerve regeneration, the gut microbiome, and accumulations of amyloid-ß and tau proteins. The present study reviews possible molecular mechanisms underpinning the therapeutic effects of fasting in patients with AD, as well as in models of the disorder, to establish a theoretical basis for using fasting as a viable approach to treat AD. [ABSTRACT FROM AUTHOR]

The main purpose of the present study was to assess the beneficial effect of Lactobacillus plantarum GM11 (LacP GM11), screened from Sichuan traditional fermented food, in depressive rats induced by chronic unpredictable mild stress (CUMS). Male SPF SD rats were randomly assigned to 3 groups: the control group, CUMS group and CUMS + LacP GM11 group (n = 10). The rats in the CUMS and LacP GM11 groups received CUMS stimulation for 42 d. The behavioral tests and levels of monoamine neurotransmitter, glucocorticoid hormone and brain-derived neurotrophic factor (BDNF) in the serum and hippocampus were measured. The effects of LacP GM11 on the mRNA and protein expression of BDNF and cAMP response element binding protein (CREB) in the hippocampus were also investigated. After supplementation for 21 d, LacP GM11 was associated with alleviation of depressive-like behavior, not anxiety-like behavior, in depressive rats. LacP GM11 increased the levels of 5-hydroxytryptamine (5-HT) and BDNF and decreased the level of cortisol (CORT) in the serum and hippocampus in depressed rats. In addition, treatment with LacP GM11 also increased the mRNA and protein expression of BDNF and CREB in the hippocampus. This work has revealed that LacP GM11 has potential beneficial effects on depression. This effect might be related to alleviating monoamine neurotransmitter deficiency, HPA axis hyperfunction and CREB-BDNF signaling pathway downregulation. This study demonstrates that LacP GM11 could be a potential therapeutic approach to treat depression and other mental health problems. [ABSTRACT FROM AUTHOR]

Anxiety or depression after percutaneous coronary intervention (PCI) is one of the key clinical problems in cardiology that need to be solved urgently. Brain-derived neurotrophic factor (BDNF) may be a potential biomarker for the pathogenesis and treatment of anxiety or depression after PCI. This article reviews the correlation between BDNF and cardiovascular system and nervous system from the aspects of synthesis, release and action site of BDNF, and focuses on the latest research progress of the mechanism of BDNF in anxiety or depression after PCI. It includes the specific mechanisms by which BDNF regulates the levels of inflammatory factors, reduces oxidative stress damage, and mediates multiple signaling pathways. In addition, this review summarizes the therapeutic potential of BDNF as a potential biomarker for anxiety or depression after PCI. [ABSTRACT FROM AUTHOR]

This study investigates the combined effects of the neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31-Pro34]NPY at a dose of 132 µg and Ketamine at 10 mg/Kg on cognitive functions and neuronal proliferation, against a backdrop where neurodegenerative diseases present an escalating challenge to global health systems. Utilizing male Sprague-Dawley rats in a physiological model, this research employed a single-dose administration of these compounds and assessed their impact 24 h after treatment on object-in-place memory tasks, alongside cellular proliferation within the dorsal hippocampus dentate gyrus. Methods such as the in situ proximity ligation assay and immunohistochemistry for proliferating a cell nuclear antigen (PCNA) and doublecortin (DCX) were utilized. The results demonstrated that co-administration significantly enhanced memory consolidation and increased neuronal proliferation, specifically neuroblasts, without affecting quiescent neural progenitors and astrocytes. These effects were mediated by the potential formation of NPY1R-TrkB heteroreceptor complexes, as suggested by receptor co-localization studies, although further investigation is required to conclusively prove this interaction. The findings also highlighted the pivotal role of brain-derived neurotrophic factor (BDNF) in mediating these effects. In conclusion, this study presents a promising avenue for enhancing cognitive functions and neuronal proliferation through the synergistic action of the NPY1R agonist and Ketamine, potentially via NPY1R-TrkB heteroreceptor complex formation, offering new insights into therapeutic strategies for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Here, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7‐day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin‐1, LC3, p62 and cleaved caspase‐3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin‐1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase‐3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin‐1, LC3 and p62 and inhibiting the apoptotic caspase‐3 protein while its beneficial effects were apparent in neurological tests from the 4th day. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic catalyzed the swift development and distribution of mRNA vaccines, including BNT162b2, to address the disease. Concerns have arisen about the potential neurodevelopmental implications of these vaccines, especially in susceptible groups such as pregnant women and their offspring. This study aimed to investigate the gene expression of WNT, brain-derived neurotrophic factor (BDNF) levels, specific cytokines, m-TOR expression, neuropathology, and autism-related neurobehavioral outcomes in a rat model. Pregnant rats received the COVID-19 mRNA BNT162b2 vaccine during gestation. Subsequent evaluations on male and female offspring included autism-like behaviors, neuronal counts, and motor performance. Molecular techniques were applied to quantify WNT and m-TOR gene expressions, BDNF levels, and specific cytokines in brain tissue samples. The findings were then contextualized within the extant literature to identify potential mechanisms. Our findings reveal that the mRNA BNT162b2 vaccine significantly alters WNT gene expression and BDNF levels in both male and female rats, suggesting a profound impact on key neurodevelopmental pathways. Notably, male rats exhibited pronounced autism-like behaviors, characterized by a marked reduction in social interaction and repetitive patterns of behavior. Furthermore, there was a substantial decrease in neuronal counts in critical brain regions, indicating potential neurodegeneration or altered neurodevelopment. Male rats also demonstrated impaired motor performance, evidenced by reduced coordination and agility. Our research provides insights into the effects of the COVID-19 mRNA BNT162b2 vaccine on WNT gene expression, BDNF levels, and certain neurodevelopmental markers in a rat model. More extensive studies are needed to confirm these observations in humans and to explore the exact mechanisms. A comprehensive understanding of the risks and rewards of COVID-19 vaccination, especially during pregnancy, remains essential. [ABSTRACT FROM AUTHOR]

The PTEN gene negatively regulates the oncogenic PI3K-AKT pathway by encoding a lipid and protein phosphatase that dephosphorylates lipid phosphatidylinositol-3,4,5-triphosphate (PIP3) resulting in the inhibition of PI3K and downstream inhibition of AKT. Overexpression of PTEN in mice leads to a longer lifespan compared to control littermates, although the mechanism is unknown. Here, we provide evidence that young adult PTENOE mice exhibit many characteristics shared by other slow-aging mouse models, including those with mutations that affect GH/IGF1 pathways, calorie-restricted mice, and mice treated with anti-aging drugs. PTENOE white adipose tissue (WAT) has increased UCP1, a protein linked to increased thermogenesis. WAT of PTENOE mice also shows a change in polarization of fat-associated macrophages, with elevated levels of arginase 1 (Arg1, characteristic of M2 macrophages) and decreased production of inducible nitric oxide synthase (iNOS, characteristic of M1 macrophages). Muscle and hippocampus showed increased expression of the myokine FNDC5, and higher levels of its cleavage product irisin in plasma, which has been linked to increased conversion of WAT to more thermogenic beige/brown adipose tissue. PTENOE mice also have an increase, in plasma and liver, of GPLD1, which is known to improve cognition in mice. Hippocampus of the PTENOE mice has elevation of both BDNF and DCX, indices of brain resilience and neurogenesis. These changes in fat, macrophages, liver, muscle, hippocampus, and plasma may be considered "aging rate indicators" in that they seem to be consistently changed across many of the long-lived mouse models and may help to extend lifespan by delaying many forms of late-life illness. Our new findings show that PTENOE mice can be added to the group of long-lived mice that share this multi-tissue suite of biochemical characteristics. [ABSTRACT FROM AUTHOR]

Historically, progesterone has been studied significantly within the context of reproductive biology. However, there is now an abundance of evidence for its role in regions of the central nervous system (CNS) associated with such nonreproductive functions that include cognition and affect. Here, we describe mechanisms of progesterone action that support its brain-protective effects, and focus particularly on the role of neurotrophins (such as brain-derived neurotrophic factor, BDNF), the receptors that are critical for their regulation, and the role of certain microRNA in influencing the brain-protective effects of progesterone. In addition, we describe evidence to support the particular importance of glia in mediating the neuroprotective effects of progesterone. Through this review of these mechanisms and our own prior published work, we offer insight into why the effects of a progestin on brain protection may be dependent on the type of progestin (e.g., progesterone versus the synthetic, medroxyprogesterone acetate) used, and age, and as such, we offer insight into the future clinical implication of progesterone treatment for such disorders that include Alzheimer's disease, stroke, and traumatic brain injury. [ABSTRACT FROM AUTHOR]

This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination. [ABSTRACT FROM AUTHOR]

Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55–90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This single-center study aimed to explore the relationship between lipid profiles and BDNF levels in 90 patients who had experienced AIS for the first time. The results show that the high BDNF group (≥3.227 ng/mL) had significantly higher HbA1C and TG levels; ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C; and percentage of hyperlipidemia (60%) as well as lower levels of HDL-C, with an OR of 1.903 (95% CI: 1.187–3.051) for TG/HDL-C, 1.975 (95% CI: 1.188–3.284) for TC/HDL-C, and 2.032 (95% CI: 1.113–3.711) for LDL-C/HDL-C. Plasma BDNF levels were found to be significantly positively correlated with TG and negatively with HDL-C, with OR values of 1.017 (95% CI: 1.003–1.030) and 0.926 (95% CI: 0.876–0.978), respectively. TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C ratios are associated with BDNF levels in AIS patients. The results also indicate that, in AIS patients, higher BDNF levels are associated with lower HDL and higher TG concentrations. [ABSTRACT FROM AUTHOR]

In female mammals, the proliferation and apoptosis of granulosa cells (GCs) are critical in determining the fate of follicles and are influenced by various factors, including brain-derived neurotrophic factor (BDNF). Previous research has shown that BDNF primarily regulates GC proliferation through the PI3K/AKT, NF-kB, and CREB tumour pathways; however, the role of other molecular mechanisms in mediating BDNF-induced GC proliferation remains unclear. In this study, we investigated the involvement of the m6A reader YTH domain-containing family member 2 (YTHDF2) in BDNF-stimulated GC proliferation and its underlying mechanism. GCs were cultured in DMEM medium supplemented with varying BDNF concentrations (0, 10, 30, 75, and 150 ng/mL) for 24 h. The viability, number, and cell cycle of GCs were assessed using the CCK-8 assay, cell counting, and flow cytometry, respectively. Further exploration into YTHDF2's role in BDNF-stimulated GC proliferation was conducted using RT-qPCR, Western blotting, and sequencing. Our findings indicate that YTHDF2 mediates the effect of BDNF on GC proliferation. Additionally, this study suggests for the first time that BDNF promotes YTHDF2 expression by increasing the phosphorylation level of the ERK1/2 signalling pathway. This study offers a new perspective and foundation for further elucidating the mechanism by which BDNF regulates GC proliferation. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a neurodegenerative disease that causes physical damage to neuronal connections, leading to brain atrophy. This disruption of synaptic connections results in mild to severe cognitive impairments. Unfortunately, no effective treatment is currently known to prevent or reverse the symptoms of AD. The aim of this study was to investigate the effects of three synthetic peptides, i.e., KLVFF, RGKLVFFGR and RIIGL, on an AD in vitro model represented by differentiated SH-SY5Y neuroblastoma cells exposed to retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). The results demonstrated that RIIGL peptide had the least significant cytotoxic activity to normal SH-SY5Y while exerting high cytotoxicity against the differentiated cells. The mechanism of RIIGL peptide in the differentiated SH-SY5Y was investigated based on changes in secretory proteins compared to another two peptides. A total of 380 proteins were identified, and five of them were significantly detected after treatment with RIIGL peptide. These secretory proteins were found to be related to microtubule-associated protein tau (MAPT) and amyloid-beta precursor protein (APP). RIIGL peptide acts on differentiated SH-SY5Y by regulating amyloid-beta formation, neuron apoptotic process, ceramide catabolic process, and oxidative phosphorylation and thus has the potentials to treat AD.

Background: Impulsivity assessment may serve as a valuable clinical tool in the stratification of suicide risk. Acting without forethought is a crucial feature in the psychopathology of many psychiatric disturbances and corresponds with suicidal ideations, behaviors, and attempts. Methods: We present data on biological and psychological correlates of impulsivity among young adults (n = 47). Psychological analysis included both the self-description questionnaire—Barratt Impulsiveness Scale (BIS-11)—and neuropsychological behavioral tests, including the Iowa Gambling Task (IGT), the Simple Response Time task (SRT), and the Continuous Performance Test (CPT). mRNA and micro-RNA were isolated from peripheral blood mononuclear cells (PBMC). Expression levels of Brain-Derived Neurotrophic Factor (BDNF) mRNA and its regulatory micro RNAs, mir-1-3p, mir-15a-5p, mir-26a-5p, mir-26b-5p, and mir-195-5p, were analyzed using the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. proBDNF and BDNF plasma protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Significant correlations between BDNF mRNA and mir-15a-5p as well as proBDNF levels and mir-1-3p were detected. proBDNF protein levels correlated with motor and perseverance, while mir-26b correlated with cognitive complexity subdimensions of the BIS-11 scale. Correlations between BDNF, miRNAs, and the results of neuropsychological tests were also detected. Conclusions: The BDNF pathway shows a clinical potential in searching for biomarkers of impulse-control impairment. BDNF-regulatory micro-RNAs are detectable and related to clinical parameters in the studied population, which needs further research.

Abstract Background Alzheimer’s disease (AD) is an age-related disease characterized by altered cognition, neuroinflammation, and neurodegeneration against which there is presently no effective cure. Brain-derived neurotrophic factor (BDNF) is a key neurotrophin involved in the learning and memory process, with a crucial role in synaptic plasticity and neuronal survival. Several findings support that a reduced BDNF expression in the human brain is associated with AD pathogenesis. BDNF has been proposed as a potential therapy for AD, but BDNF has low brain penetration. In this study, we used an innovative encapsulated cell biodelivery (ECB) device, containing genetically modified cells capable of releasing BDNF and characterized its feasibility and therapeutic effects in the novel App knock-in AD mouse model (App NL−G−F ). Methods ECB’s containing human ARPE-19 cells genetically modified to release BDNF (ECB-BDNF devices) were stereotactically implanted bilaterally into hippocampus of 3-month-old App NL−G−F mice. The stability of BDNF release and its effect on AD pathology were evaluated after 1, 2-, and 4-months post-implantation by immunohistochemical and biochemical analyses. Exploratory and memory performance using elevated plus maze (EPM) and Y-maze test were performed in the 4-months treatment group. Immunological reaction towards ECB-BDNF devices were studied under ex vivo and in vivo settings. Results The surgery and the ECB-BDNF implants were well tolerated without any signs of unwanted side effects or weight loss. ECB-BDNF devices did not induce host-mediated immune response under ex vivo set-up but showed reduced immune cell attachment when explanted 4-months post-implantation. Elevated BDNF staining around ECB-BDNF device proximity was detected after 1, 2, and 4 months treatment, but the retrieved devices showed variable BDNF release. A reduction of amyloid-β (Aβ) plaque deposition was observed around ECB-BDNF device proximity after 2-months of BDNF delivery. Conclusions The result of this study supports the use of ECB device as a promising drug-delivery approach to locally administer BBB-impermeable factors for treating neurodegenerative conditions like AD. Optimization of the mouse-sized devices to reduce variability of BDNF release is needed to employ the ECB platform in future pre-clinical research and therapy development studies.

The consequence of appropriate food consumption and the corresponding amount of dietary nutrients on brain function is widely recognized. More and more studies are pointing to the importance of diet for alleviating neurological symptoms associated with a wide range of clinical disorders. The recently discovered implications of nutritional variables on modifications in mitochondrial dysfunction, epigenetic modification, and neurological inflammation represent important factors that play a crucial role in determining the effect of nutrition on Neuronal (health). This overview investigates the present state of evidence regarding the efficacy of various dietary interventions, such as dietary supplements and dietary restrictions, for in the context of managing disorders related to the brain. Particularly, it clearly state the consequences of these interventions on conditions such as Alzheimer's, Parkinson's, ischemic stroke, seizures, injury to the brain, amyotrophic lateral sclerosis (ALL), Huntington's syndrome, and multiple sclerosis (MS). Along with this, it is important to note that a variety of possible processes, such as metabolic regulation, epigenetic alteration, and the inflammation of neurons assume a pivotal function. in determining the impact of nutrition availability on the risk of neurologic conditions and treatment outcomes. Along with this, authors clearly state the innovative concept that dietary supplement intervention can modify interconnected processes of metabolism, epigenetics, and immunology, thereby addressing brain dysfunction. Concentrating on metabolic processes the study of the epigenetic-immunity network has the potential to provide a novel framework for addressing vulnerabilities in the field of neurology.