Role Of Brain-derived Neurotrophic Factor Research Articles

The Impact of Acute Mild Normobaric Hypoxia and a Single Bout of Exercise to Volitional Exhaustion on Cognitive Performance in Endurance and Strength-Trained Athletes: The role of BDNF, EP-1, Catecholamines and Lactate.

The aim of the study was to examine whether a single bout of exercise to volitional exhaustion, performed under moderate normobaric hypoxia (H), would affect psychomotor performance (PP) in differently trained athletes. For this purpose, ten strength-trained (S) athletes, ten endurance-trained (E) athletes and ten healthy men leading a sedentary lifestyle as a control (C) group performed voluntarily two graded exercise tests until volitional exhaustion (EVE) under normoxia (N) and H (FiO2 = 14.7%). We measured the peripheral level of the brain derived neurotrophic factor (BDNF), choice reaction time (CRT) and the number of correct reactions (NCR) as indices of PP. Psychomotor tests were performed at rest, immediately after the EVE and 3 minutes after the EVE. Venous blood samples were collected at rest, immediately after cessation of each EVE, and 1 h after each EVE. The results showed that the EVE significantly (p < 0.05) impaired CRT under N and H, and NCR under H only in the E group. The higher WRmax in the E compared to the S and C groups was associated with a significant (p < 0.005) increase in adrenaline (A) and noradrenaline (NA). There were no significant differences between conditions (N vs. H) in the BDNF at rest and after exercise. The EVE impaired cognitive function only in the E group; higher involvement of the sympathetic nervous system, A and NA may also play a role in this phenomenon. Therefore, it can be concluded that exposure to H did not have a negative impact on CRT or NCR. Moreover, BDNF did not improve cognitive function.

Increased levels of brain-derived neurotrophic factor in cultures of nervous cells treated with a selective serotonin reuptake inhibitor

Introduction. The effects of antidepressants such as fluoxetine on brain plasticity are associated with increased transcription and signaling of trophic factors such as brain-derived neurotrophic factor (BDNF), which enhances synaptic and neurogenic processes. Objective. To evaluate whether treatment with fluoxetine could increase BDNF levels in retinal cells. Method. To conduct the experiment, retinas were dissected from neonatal rats and cultured in complete culture medium. Next, the cultures designated for the experimental group were treated with 1µM of fluoxetine and maintained for 2, 12, 24, 48, or 72 hours in vitro. The cultures designated for the control group underwent the same protocol, but did not receive the fluoxetine treatment. The levels of BDNF were determined by Western blot analysis, and the data were analyzed by Student's t-test to compare the two groups (control and experimental). Results. The results showed that cultures treated with fluoxetine for 12, 24, and 48 hours had significantly higher levels of BDNF than the control group. Conclusion. The findings suggest that treatment with fluoxetine may have potential therapeutic effects on retinal cells by increasing BDNF levels. This adds to the existing evidence on the role of BDNF in mediating the therapeutic effects of antidepressants and highlights the potential for further research on the use of antidepressants in the treatment of retinal diseases.

Revisiting the expression of BDNF and its receptors in mammalian development.

Brain-derived neurotrophic factor (BDNF) promotes the survival and functioning of neurons in the central nervous system and contributes to proper functioning of many non-neural tissues. Although the regulation and role of BDNF have been extensively studied, a rigorous analysis of the expression dynamics of BDNF and its receptors TrkB and p75NTR is lacking. Here, we have analyzed more than 3,600 samples from 18 published RNA sequencing datasets, and used over 17,000 samples from GTEx, and ~ 180 samples from BrainSpan database, to describe the expression of BDNF in the developing mammalian neural and non-neural tissues. We show evolutionarily conserved dynamics and expression patterns of BDNF mRNA and non-conserved alternative 5' exon usage. Finally, we also show increasing BDNF protein levels during murine brain development and BDNF protein expression in several non-neural tissues. In parallel, we describe the spatiotemporal expression pattern of BDNF receptors TrkB and p75NTR in both murines and humans. Collectively, our in-depth analysis of the expression of BDNF and its receptors gives insight into the regulation and signaling of BDNF in the whole organism throughout life.

Spontaneously hypertensive rats vs. Wistar Kyoto and Wistar rats: An assessment of anxiety, motor activity, memory performance, and seizure susceptibility

Spontaneously hypertensive rats (SHRs) are widely accepted for modeling essential hypertension and Attention deficit hyperactivity disorder (ADHD). However, data concerning central nervous system changes associated with behavioral responses of this strain and usage of Wistar Kyoto (WKY) rats as controls are confounding. The objective of the present study was to assess the impact of anxiety and motor activity on the cognitive responses of SHRs compared to Wistar and WKY rats. In addition, the role of brain-derived neurotrophic factor (BDNF) in the hippocampus on cognitive behavior and seizure susceptibility in the three strains was evaluated. In Experiment#1, SHR demonstrated impulsive responses in the novelty suppression feeding test accompanied by impaired spatial working and associative memory in the Y maze and object recognition test compared with the Wistar rat but not WKY rats. In addition, the WKY rats exhibited diminished activity compared to Wistar rats in an actimeter. In Experiment#2, the seizure susceptibility was assessed by 3-min electroencephalographic (EEG) recording after two consecutive injections of pentylenetetrazol (PTZ) (20+40 mg/kg). The WKY rats were more vulnerable to rhythmic metrazol activity (RMA) than the Wistar rats. In contrast, Wistar rats were more prone to generalized tonic-clonic seizures (GTCS) than WKY rats and SHRs. Control SHR had lower BDNF expression in the hippocampus compared to Wistar rats. However, while the BDNF levels were elevated in the Wistar and WKY rats after PTZ injection, no change in this signaling molecule was observed in the SHR in the seizure condition. The results suggest Wistar rats as a more appropriate control of SHR than WKY rats for studying memory responses mediated by BDNF in the hippocampus. The higher vulnerability to seizures in Wistar and WKY rats compared to SHR might be linked to PTZ-induced decreased expression of BDNF in the hippocampus.

Brain-derived neurotrophic factor: Its role in energy balance and cancer cachexia

Brain-derived neurotrophic factor (BDNF) plays an important role in the development of the central and peripheral nervous system during embryogenesis. In the mature central nervous system, BDNF is required for the maintenance and enhancement of synaptic transmissions and the survival of neurons. Particularly, it is involved in the modulation of neurocircuits that control energy balance through food intake, energy expenditure, and locomotion. Regulation of BDNF in the central nervous system is complex and environmental factors affect its expression in murine models which may reflect to phenotype dramatically. Furthermore, BDNF and its high-affinity receptor tropomyosin receptor kinase B (TrkB), as well as pan-neurotrophin receptor (p75NTR) is expressed in peripheral tissues in adulthood and their signaling is associated with regulation of energy balance. BDNF/TrkB signaling is exploited by cancer cells as well and BDNF expression is increased in tumors. Intriguingly, previously demonstrated roles of BDNF in regulation of food intake, adipose tissue and muscle overlap with derangements observed in cancer cachexia. However, data about the involvement of BDNF in cachectic cancer patients and murine models are scarce and inconclusive. In the future, knock-in and/or knock-out experiments with murine cancer models could be helpful to explore potential new roles for BDNF in the development of cancer cachexia.

Brain-derived neurotrophic factor contributes to neurogenesis after intracerebral hemorrhage: a rodent model and human study.

Intracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF). A rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA). In the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume. BDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH.

The Role of BDNF as a Biomarker in Cognitive and Sensory Neurodegeneration.

Brain-derived neurotrophic factor (BDNF) has a crucial function in the central nervous system and in sensory structures including olfactory and auditory systems. Many studies have highlighted the protective effects of BDNF in the brain, showing how it can promote neuronal growth and survival and modulate synaptic plasticity. On the other hand, conflicting data about BDNF expression and functions in the cochlear and in olfactory structures have been reported. Several clinical and experimental research studies showed alterations in BDNF levels in neurodegenerative diseases affecting the central and peripheral nervous system, suggesting that BDNF can be a promising biomarker in most neurodegenerative conditions, including Alzheimer's disease, shearing loss, or olfactory impairment. Here, we summarize current research concerning BDNF functions in brain and in sensory domains (olfaction and hearing), focusing on the effects of the BDNF/TrkB signalling pathway activation in both physiological and pathological conditions. Finally, we review significant studies highlighting the possibility to target BDNF as a biomarker in early diagnosis of sensory and cognitive neurodegeneration, opening new opportunities to develop effective therapeutic strategies aimed to counteract neurodegeneration.

BDNF Val66Met polymorphism is associated with consolidation of episodic memory during sleep

The brain-derived neurotrophic factor (BDNF) is an essential regulator of synaptic plasticity, a candidate neurobiological mechanism underlying learning and memory. A functional polymorphism in the BDNF gene, Val66Met (rs6265), has been linked to memory and cognition in healthy individuals and clinical populations. Sleep contributes to memory consolidation, yet information about the possible role of BDNF in this process is scarce. To address this question, we investigated the relationship between the BDNF Val66Met genotype and consolidation of episodic declarative and procedural (motor) non-declarative memories in healthy adults. The carriers of Met66 allele, as compared with Val66 homozygotes, showed stronger forgetting overnight (24 h after encoding), but not over shorter time (immediately or 20 min after word list presentation). There was no effect of Val66Met genotype on motor learning. These data suggest that BDNF plays a role in neuroplasticity underlying episodic memory consolidation during sleep.

Role of BDNF in neuroplasticity associated with alcohol dependence

Chronic alcohol consumption is characterized by disturbances of neuroplasticity. Brain-derived neurotrophic factor (BDNF) may mechanistically participate in this process. Here we aimed to review actual experimental and clinical data related to BDNF involvement in neuroplasticity in the context of alcohol dependence. As shown in experiments on the rodents alcohol consumption is accompanied brain region-specific changes of BDNF expression and by structural and behavioral impairments. BDNF reverses aberrant neuroplasticity during alcohol intoxication. According to clinical data indices characterized BDNF demonstrate close relationship with consequences of alcohol dependence. Polymorphism rs6265 within BDNF gene interacts with macrostructural changes in the brain, while peripheral BDNF concentration may reflect anxiety, depression and cognitive decline. Thus, BDNF is involved in mechanisms of alcohol-related aberrant neuroplasticity, while polymorphisms within BDNF gene and peripheral BDNF concentration may be biomarkers, diagnostic or prognostic factors in clinics of alcoholism.

Pathoclinical associations between panic disorders and the brain-derived neurotrophic factor Val66Met polymorphism: an updated meta-analysis.

Prior studies have indicated the pathological role of brain-derived neurotrophic factor (BDNF) gene polymorphism in panic disorders (PD). A functionally less active BDNF Val66Met mutant was previously detected in PD patients with different ethnic backgrounds. However, the results remain inconclusive or inconsistent. A meta-analysis was used to explore the consistency of the BDNF Val66Met mutant's association with PD irrespective of the subject's ethnicity. Relevant case-controlled full-length clinical and preclinical reports were retrieved by database searching, and 11 articles involving 2203 cases and 2554 controls were systematically selected per the standard inclusion criteria. Eleven articles were finally included that explored the relationship between the Val66Met polymorphism and PD risk susceptibility. Statistical analysis revealed a significant genetic association of the mutation, allele frequencies, and genotype distributions of BDNF with PD onset. Our findings demonstrated that the BDNF Val66Met is a susceptibility factor of PD.

Chronic haloperidol administration downregulates select BDNF transcript and protein levels in the dorsolateral prefrontal cortex of rhesus monkeys.

Post-mortem studies in the prefrontal cortex and hippocampal formation from schizophrenia patients have revealed significant disruptions in the expression molecules associated with cytoarchitecture, synaptic structure, function, and plasticity, known to be regulated in part by brain derived neurotrophic factor (BDNF). Interestingly, several studies using postmortem brain tissue from individuals diagnosed with schizophrenia have revealed a significant reduction in BDNF mRNA and protein levels in the dorsolateral prefrontal cortex (DLPFC), hippocampus and related areas; however, differentiating the effects of illness from antipsychotic history has remained difficult. We hypothesized that chronic antipsychotic treatment may contribute to the altered BDNF mRNA and protein expression observed in post-mortem brains of individuals diagnosed with schizophrenia. To address the influence of antipsychotic administration on BDNF expression in the primate brain, rhesus monkeys orally administered haloperidol, clozapine, or vehicle twice daily for 180 days. We found BDNF splice variants 4 and 5 in the DLPFC and variant 2 in the EC were significantly down-regulated following chronic administration of haloperidol. In addition, proBDNF and mature BDNF expression in the DLPFC, but not the EC, were significantly reduced. Based on the known regulation of BDNF expression by BDNF-AS, we assessed the expression of this lncRNA and found expression was significantly upregulated in the DLPFC, but not EC. The results of the present study provide evidence of haloperidol-induced regulation of BDNF mRNA and protein expression in the DLFPC and suggest an important role for BDNF-AS in this regulation. Given the role of BDNF in synaptic plasticity, neuronal survival and maintenance, aberrant expression induced by haloperidol likely has significant ramifications for neuronal populations and circuits in primate cortex.

The Role of Brain-Derived Neurotrophic Factor (BDNF) in Diagnosis and Treatment of Epilepsy, Depression, Schizophrenia, Anorexia Nervosa and Alzheimer's Disease as Highly Drug-Resistant Diseases: A Narrative Review.

Brain-derived neurotrophic factor (BDNF) belongs to the family of neurotrophins, which are growth factors with trophic effects on neurons. BDNF is the most widely distributed neurotrophin in the central nervous system (CNS) and is highly expressed in the prefrontal cortex (PFC) and hippocampus. Its distribution outside the CNS has also been demonstrated, but most studies have focused on its effects in neuropsychiatric disorders. Despite the advances in medicine in recent decades, neurological and psychiatric diseases are still characterized by high drug resistance. This review focuses on the use of BDNF in the developmental assessment, treatment monitoring, and pharmacotherapy of selected diseases, with a particular emphasis on epilepsy, depression, anorexia, obesity, schizophrenia, and Alzheimer's disease. The limitations of using a molecule with such a wide distribution range and inconsistent method of determination are also highlighted.

Genetic Val66Met BDNF Variant Increases Hyperphagia on Fat-rich Diets in Mice.

High prevalence of obesity is attributable in part to consumption of highly palatable, fat-rich foods. However, the mechanism controlling dietary fat intake is largely unknown. In this study we investigated the role of brain-derived neurotrophic factor (BDNF) in the control of dietary fat intake in a mouse model that mimics the common human Val-to-Met (Val66Met) polymorphism that impairs BDNF release via the regulated secretory pathway. BdnfMet/Met mice gained weight much faster than wild-type (WT) mice and developed severe obesity due to marked hyperphagia when they were fed HFD. Hyperphagia in these mice worsened when the fat content in their diet was increased. Conversely, mice lacking leptin exhibited similar hyperphagia on chow and HFD. When 2 diets were provided simultaneously, WT and BdnfMet/Met mice showed a comparable preference for the more palatable diet rich in either fat or sucrose, indicating that increased hyperphagia on fat-rich diets in BdnfMet/Met mice is not due to enhanced hedonic drive. In support of this interpretation, WT and BdnfMet/Met mice increased calorie intake to a similar extent during the first day after chow was switched to HFD; however, WT mice decreased HFD intake faster than BdnfMet/Met mice in subsequent days. Furthermore, we found that refeeding after fasting or nocturnal feeding with HFD activated TrkB more strongly than with chow in the hypothalamus of WT mice, whereas TrkB activation under these 2 conditions was greatly attenuated in BdnfMet/Met mice. These results indicate that satiety factors generated during HFD feeding induce BDNF release to suppress excess dietary fat intake.

The role of BDNF in the clinical course of primary headaches

Objective: Brain-derived neurotrophic factor (BDNF) is associated with the pathophysiology of primary headaches. The present study aimed to investigate interictal and ictal BDNF levels and its association with clinical parameters in patients with primary headaches. Methods: Three groups of headache patients enrolled in this study: patients with episodic migraine with and without aura, cluster headaches, and tension-type headaches according to the current criteria of the International Headache Society. In migraine patients and cluster headache patients, venous blood samples were collected twice: outside and during attacks. In patients with tension-type headaches and healthy controls, one single blood sample was taken. The research comprised 120 patients (males and females) suffering from primary headaches. The control group consisted of 30 healthy volunteers. Results: This is the first study to show that there is no gender difference BDNF levels in Uzbek patients with primary headaches. Migraine and cluster headache patients revealed significantly higher BDNF serum levels during headache attacks compared with attack-free periods ( p &lt; 0.02). Conclusion: This reinforces the view that BDNF may be implicated in the pathophysiology of primary headaches.

The Association between Brain-Derived Neurotrophic Factor (BDNF) Protein Level and Body Mass Index.

Background and Objectives: Obesity is a major health concern worldwide. Many studies emphasize the important role of brain-derived neurotrophic factor (BDNF) in regulating appetite and body weight. We aimed to investigate the association between BDNF protein serum levels and body mass index (BMI). Materials and Methods: We conducted a cross-sectional study among 108 healthy adult participants divided into six categories depending on their body mass index (BMI). The ages of the participants ranged between 21 to 45 years. The BDNF serum level was measured using the enzyme-linked immunosorbent assay (ELISA) technique. Results: A Kruskal-Wallis test showed a significant difference in BDNF between the different BMI categories, χ2(2) = 24.201, p &lt; 0.001. Our data also showed that BDNF levels were significantly lower in people with obesity classes II and III than those of normal weight (p &lt; 0.05). The Spearman rank correlation test was statistically significant with negative correlations between the BMI and BDNF (r) = -0.478, (p &lt; 0.01). Moreover, we observed a negative dose-dependent relationship pattern between BMI categories and the levels of circulating BDNF protein. Conclusions: In this study, our data support the hypothesis that low serum levels of BDNF are associated with high BMI and obesity in Saudi adults.

Correlation between nocturnal intermittent hypoxemia and mild cognitive impairment in the older adult and the role of BDNF Val66Met polymorphism: a hospital-based cross-sectional study.

To explore theprevalence ofnocturnal intermittent hypoxemia (NIH) in a tertiary hospital geriatric department and the relationship between NIH and mild cognitive impairment (MCI) in older adults, and to examinethe role of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. Older adults aged ≥ 60 were enrolled. NIH and cognitive assessments were conducted. BDNF concentrations and BDNF Val66Met polymorphism were detected for a preliminary exploration of the possible mechanism of the process. Of 325 older adults enrolled, 157 (48%) had NIH and were further divided into mild, moderate, and severe NIH groups according to their oxygen desaturation of ≥ 4% per hour of sleep (ODI4). MCI detection rate in the four groups gradually increased, and the differences were statistically significant (chi-square = 4.457, P = 0.035). ODI4 was negatively correlated with MoCA score in all participants (r = - 0.115, P = 0.039) and patients with NIH (r = - 0.199, P = 0.012). After adjusting for sex, age, and cardiovascular risk factors, NIH and MCI remained independently associated (OR = 3.13, 95% CI 1.03-9.53, P = 0.045). BDNF levels were positively correlated with MoCA score (r = 0.169, P = 0.028) and negatively correlated with nocturnal average oxygen saturation in patients with NIH (r = - 0.288, P = 0.008). Older adults with different BDNF Val66Met genotypes did not show significant differences in MCI rate and BDNF levels (P > 0.05). The older adults with NIH have a higher MCI detection rate. BDNF levels may be a potential biomarker for cognitive dysfunction in patients with NIH.

Empagliflozin enhances neuroplasticity in rotenone-induced parkinsonism: Role of BDNF, CREB and Npas4

AimsParkinsonism is characterized by degeneration of dopaminergic neurons and impairment in neuroplasticity. Empagliflozin (EMPA) is an anti-diabetic drug that has been shown to improve cognitive dysfunctions and exerted antioxidant and anti-inflammatory effects in different models. This study aimed to determine the neuroprotective effects of EMPA against rotenone (ROT)-induced parkinsonism. Main methodsROT (1.5 mg/kg) was injected subcutaneously three times per week for two successive weeks. Mice were treated with EMPA (3 and 10 mg/kg, orally) for one week prior ROT administration and for another two weeks along with ROT. After that, motor functions and histopathological changes were assessed, and brains were isolated for biochemical analyses and immunohistochemical investigation. Key findingsResults indicated that, in a dose dependent manner, EMPA improved motor functions and histopathological changes induced by ROT, increased brain content of reduced glutathione (GSH), dopamine (DA), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear factor erythroid 2–related factor 2 (Nrf2), inositol trisphosphate (IP3), calcium (Ca2+), calcium/calmodulin-dependent protein kinase type IV (CaMKIV) and phospho-Protein kinase B (p-Akt) levels compared to ROT group. Additionally, EMPA decreased the levels of malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α), and inactivated glycogen synthase kinase-3 beta (GSK-3β). Improvement in neuroplasticity was also observed indicated by elevation in brain derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and neuronal PAS domain Protein 4 (Npas4). SignificanceEMPA improved motor functions possibly through improving neuroplasticity markers and antioxidant, anti-inflammatory, and neuroprotective effects in a dose dependent manner.

A meta-analysis on the role of brain-derived neurotrophic factor in Parkinson's disease patients.

Brain-derived neurotrophic factor (BDNF) is essential for the development of dopaminergic neurons in the substantia nigra. To investigate the level of BDNF among Parkinson's disease (PD) subjects and the influence of depression on BDNF levels. A total of 1920 subjects were included in the analysis; of these, 1034 had PD and 886 were healthy controls. A thorough literature search up to May 2022 was conducted. The mean difference (MD) of BDNF levels and 95% confidence intervals (95% CIs) were calculated with random or fixed effects models. Compared to healthy controls, levels of BDNF were significantly lower in patients with PD (MD = -1.60, 95% CI (-2.49, -0.70), p < 0.001). Patients with PD and depression had significantly lower levels of BDNF (MD = -3.39, 95% CI (-5.55, -1.23), p = 0.002), as well as those with PD without depression (MD = -0.80, 95% CI (-1.56, -0.03), p = 0.04). However, there was no discernible change in BDNF levels (MD = -0.82, 95% CI (1.75, 0.10), p = 0.08) between the participants with PD and depression compared to the PD patients alone. Compared with healthy controls, BDNF levels were significantly lower in the subjects with PD combined with depression, and PD without depression. However, there was no discernible difference in BDNF levels between subjects with PD with depression compared to those with PD without depression.

Function of brain-derived neurotrophic factor in the hypothalamus: Implications for depression pathology.

Depression is a prevalent mental health disorder and is the number one cause of disability worldwide. Risk factors for depression include genetic predisposition and stressful life events, and depression is twice as prevalent in women compared to men. Both clinical and preclinical research have implicated a critical role for brain-derived neurotrophic factor (BDNF) signaling in depression pathology as well as therapeutics. A preponderance of this research has focused on the role of BDNF and its primary receptor tropomyosin-related kinase B (TrkB) in the cortex and hippocampus. However, much of the symptomatology for depression is consistent with disruptions in functions of the hypothalamus including changes in weight, activity levels, responses to stress, and sociability. Here, we review evidence for the role of BDNF and TrkB signaling in the regions of the hypothalamus and their role in these autonomic and behavioral functions associated with depression. In addition, we identify areas for further research. Understanding the role of BDNF signaling in the hypothalamus will lead to valuable insights for sex- and stress-dependent neurobiological underpinnings of depression pathology.

Association of plasma brain-derived neurotrophic factor levels and frailty in community-dwelling older adults

Brain-derived neurotrophic factor (BDNF), an exercise-induced neurotrophin, is an important factor in memory consolidation and cognitive function. This study evaluates the association between plasma BDNF levels and frailty in community-dwelling older adults. Plasma BDNF levels were analyzed in a total of 302 individuals aged 70–84 years from the Korean Frailty and Aging Cohort Study. There were 30 (9.9%) participants with frailty. They were older and had a higher prevalence of dementia and depression than those without frailty. There were no differences in the proportion of male sex between the frail and non-frail groups. Plasma BDNF levels were significantly lower in participants with frailty than in those without frailty. The presence of frailty was significantly associated with plasma BDNF levels (odds ratio 0.508, 95% confidence interval 0.304–0.849) as well as age, hemoglobin, and the presence of dementia, and depression. After adjustment for confounding factors, the significant association between plasma BDNF and frailty was maintained (0.495, 0.281–0.874). This association remained consistent after exclusion of individuals with dementia, depression, stroke, diabetes, and osteoporosis. Plasma BDNF levels were significantly associated with frailty in community-dwelling older adults. Our study may suggest the possible role of BDNF as a novel biomarker of frailty.