Role Of Brain-derived Neurotrophic Factor Research Articles

Neuroprotective efficacy of nano-CoQ against propionic acid toxicity in rats: Role of BDNF and CREB protein expressions.

Propionic acid (PRA) is used as a food preservative. This study was aimed to investigate the neuroprotective effect of acetyl-l-carnitine (ALC) and nano-Coenzyme Q (N-CoQ) on brain intoxication induced by PRA in rats. Rats were divided into five groups: group I: control; group II: received PRA; group III: received ALC; group IV: received N-CoQ; and group V: received ALC and N-CoQ for 5 days. The antioxidants in question markedly ameliorated serum interleukin-1β and tumor necrosis factor-α, and brain NO, lipid peroxide, glutathione, and superoxide dismutase levels as well as protein expression of brain-derived neurotrophic factor (BDNF) and P-cyclic-AMP response element-binding protein (CREB) that were altered by a toxic dose of PRA, as well as histopathological alterations, including improvement of the cerebellum architecture. Interestingly, the combination therapy of ALC and N-CoQ achieved the most neuroprotective effect compared with monotherapies. The current study established that N-CoQ is considered as a useful tool to prevent brain injury induced by PRA. BDNF and CREB proteins are involved in both PRA neurotoxicity and treatment.

Neurobiology of BDNF in fear memory, sensitivity to stress, and stress-related disorders

Brain-derived neurotrophic factor (BDNF) is widely accepted for its involvement in resilience and antidepressant drug action, is a common genetic locus of risk for mental illnesses, and remains one of the most prominently studied molecules within psychiatry. Stress, which arguably remains the "lowest common denominator" risk factor for several mental illnesses, targets BDNF in disease-implicated brain regions and circuits. Altered stress-related responses have also been observed in animal models of BDNF deficiency in vivo, and BDNF is a common downstream intermediary for environmental factors that potentiate anxiety- and depressive-like behavior. However, BDNF's broad functionality has manifested a heterogeneous literature; likely reflecting that BDNF plays a hitherto under-recognized multifactorial role as both a regulator and target of stress hormone signaling within the brain. The role of BDNF in vulnerability to stress and stress-related disorders, such as posttraumatic stress disorder (PTSD), is a prominent example where inconsistent effects have emerged across numerous models, labs, and disciplines. In the current review we provide a contemporary update on the neurobiology of BDNF including new data from the behavioral neuroscience and neuropsychiatry literature on fear memory consolidation and extinction, stress, and PTSD. First we present an overview of recent advances in knowledge on the role of BDNF within the fear circuitry, as well as address mounting evidence whereby stress hormones interact with endogenous BDNF-TrkB signaling to alter brain homeostasis. Glucocorticoid signaling also acutely recruits BDNF to enhance the expression of fear memory. We then include observations that the functional common BDNF Val66Met polymorphism modulates stress susceptibility as well as stress-related and stress-inducible neuropsychiatric endophenotypes in both man and mouse. We conclude by proposing a BDNF stress-sensitivity hypothesis, which posits that disruption of endogenous BDNF activity by common factors (such as the BDNF Val66Met variant) potentiates sensitivity to stress and, by extension, vulnerability to stress-inducible illnesses. Thus, BDNF may induce plasticity to deleteriously promote the encoding of fear and trauma but, conversely, also enable adaptive plasticity during extinction learning to suppress PTSD-like fear responses. Ergo regulators of BDNF availability, such as the Val66Met polymorphism, may orchestrate sensitivity to stress, trauma, and risk of stress-induced disorders such as PTSD. Given an increasing interest in personalized psychiatry and clinically complex cases, this model provides a framework from which to experimentally disentangle the causal actions of BDNF in stress responses, which likely interact to potentiate, produce, and impair treatment of, stress-related psychiatric disorders.

A review of peripheral brain-derived neurotrophic factor levels in alcohol-dependent patients: Current understanding.

Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroplasticity of the brain, and its role in alcohol dependence has been explored in the recent past. Animal studies suggest that BDNF may function as a protective factor in transition from social drinking to an alcohol use disorder. However, clinical studies have not been able to establish similar findings and have shown mixed results. In order to obtain a comprehensive understanding, the current review aims to evaluate the existing literature on the role of BDNF in alcohol dependence. Articles were retrieved using search engines PubMed and Google Scholar. Original research studies focusing on human participants, published in English till October 2018 were reviewed. Studies which measured BDNF levels in serum or plasma or both were included in this study. A total of 13 studies were found which compared BDNF levels in alcohol-dependent patients with control population. The studies have mixed findings. Seven studies measured BDNF levels across the abstinence period, and most of the studies show improving BDNF levels across the abstinence. The current review supports the notion that BDNF plays an important role in the neuroplasticity of alcohol dependence. However, it is premature at this stage to draw conclusions that BDNF may be used as a biomarker, as there have been inconclusive findings when compared with control population. Future studies with longer follow-ups, larger sample size, comparing early and late periods of alcohol abstinence are required for better understanding of the role BDNF in alcohol dependence.

Role of BDNF in the pathophysiology and treatment of depression: Activity-dependent effects distinguish rapid-acting antidepressants.

The pathophysiology and treatment of depression have been the focus of intense research and while there is much that remains unknown, modern neurobiological approaches are making progress. This work demonstrates that stress and depression are associated with atrophy of neurons and reduced synaptic connectivity in brain regions such as the hippocampus and prefrontal cortex that contribute to depressive behaviors, and conversely that antidepressant treatment can reverse these deficits. The role of neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), has been of particular interest as these factors play a key role in activity-dependent regulation of synaptic plasticity. Here, we review the literature demonstrating that exposure to stress and depression decreases BDNF expression in the hippocampus and PFC and conversely that antidepressant treatment can up-regulate BDNF in the adult brain and reverse the effects of stress. We then focus on rapid-acting antidepressants, particularly the NMDA receptor antagonist ketamine, which produces rapid synaptic and antidepressant behavioral actions that are dependent on activity-dependent release of BDNF. This rapid release of BDNF differs from typical monoaminergic agents that require chronic administration to produce a slow induction of BDNF expression, consistent with the time lag for the therapeutic action of these agents. We review evidence that other classes of rapid-acting agents also require BDNF release, demonstrating that this is a common, convergent downstream mechanism. Finally, we discuss evidence that the actions of ketamine are also dependent on another growth factor, vascular endothelial growth factor (VEGF) and its complex interplay with BDNF.

Exercise Training Induced Changes In Nuclear Magnetic Resonance-Measured Lipid Particles In Mild Cognitively Impaired Elderly African American Volunteers: A Pilot Study.

PurposePoor cardiorespiratory fitness (CRF) is linked to cognitive deterioration, but its effects on lipid heterogeneity and functional properties in older African American (AA) subjects with mild cognitive impairment (MCI) need elucidation. This study determined whether exercise training-induced changes in blood lipid particle sizes (LPS) were associated with CRF determined by VO2Max in elderly AAs with MCI. Given the pivotal role of brain-derived neurotrophic factor (BDNF) on glucose metabolism, and therefore, “diabetic dyslipidemia”, we also determined whether changes in LPS were associated with the levels of serum BDNF.MethodsThis analysis included 17 of the 29 randomized elderly AAs with MCI who had NMR data at baseline and after a 6-month training. We used Generalized Linear Regression (GLM) models to examine cardiorespiratory fitness (VO2Max) effects on training-induced change in LPS in the stretch and aerobic groups. Additionally, we determined whether the level of BDNF influenced change in LPS.ResultsCollectively, mean VO2Max (23.81±6.17) did not differ significantly between aerobic and stretch groups (difference=3.17±3.56, P=0.495). Training-related changes in very low-density lipoprotein, chylomicrons, and total low-density lipoprotein (LDL) particle sizes correlated significantly with VO2Max, but not after adjustment for age and gender. However, increased VO2Max significantly associated with reduced total LDL particle size after similar adjustments (P = 0.046). While stretch exercise associated with increased protective large high-density lipoprotein particle size, the overall effect was not sustained following adjustments for gender and age. However, changes in serum BDNF were associated with changes in triglyceride and cholesterol transport particle sizes (P < 0.051).ConclusionPromotion of stretch and aerobic exercise to increase CRF in elderly AA volunteers with MCI may also promote beneficial changes in lipoprotein particle profile. Because high BDNF concentration may reduce CVD risk, training-related improvements in BDNF levels are likely advantageous. Large randomized studies are needed to confirm our observations and to further elucidate the role for exercise therapy in reducing CVD risk in elderly AAs with MCI.

P.498 The role of brain-derived neurotrophic factor in the biological mechanisms of burnout: epigenetic perspective

P.498 The role of brain-derived neurotrophic factor in the biological mechanisms of burnout: epigenetic perspective

Reducing luteinizing hormone levels after ovariectomy improves spatial memory: Possible role of brain-derived neurotrophic factor

Alzheimer's disease and other forms of cognitive decline are significantly more prevalent in post-menopausal women. Decreased estrogen levels, due to menopause or ovariectomy, may contribute to memory impairments and neurodegeneration. Another result of decreased estrogen levels is elevated luteinizing hormone (LH). Elevated LH after menopause/ovariectomy has been shown to impair cognition in both human and animal studies. Lowering LH levels rescues spatial memory in ovariectomized (ovx) rodents, yet the mechanisms of these effects are still unclear. Estrogens appear to exert some of their effects on memory by increasing levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. In these studies, we explored whether lowering LH may act by increasing BDNF. Ovx rats were treated with Antide, a gonadotropin releasing hormone receptor antagonist that lowers LH levels, or with estradiol. Both Antide and estradiol treatment enhanced spatial memory in ovx females. Both were found to be ineffective when a BDNF receptor antagonist was administered. Immunohistochemical analysis revealed that both Antide and estradiol increased BDNF expression in the hippocampus. Dendritic spine density on pyramidal cells in CA1 was unchanged by any treatment. These results provide evidence for a relationship between LH and BDNF in the hippocampus and demonstrate that estrogen-increasing and LH-lowering treatments may both require BDNF signaling in order to improve spatial memory.

Protective effects of vitamin D on neurophysiologic alterations in brain aging: role of brain-derived neurotrophic factor (BDNF)

ABSTRACT Background/aim: Vitamin D has been hypothesized to be main regulator of the aging rate, alongside evidences support its role in neuroprotection. However, data about the protective role of vitamin D against neurophysiologic alterations associated with brain aging is limited. This study investigated the possible protective effects that vitamin D has on brain-derived neurotrophic factor (BDNF), cholinergic function, oxidative stress and apoptosis in aging rat brain. Methods: Male Wister albino rats aged 5 months (young), 12 months (middle aged) and 24 months (old) (n = 20 each) were used. Each age group subdivided to either vitamin D3 supplementation (500 IU/kg/day orally for 5 weeks) or no supplementation (control) group (n = 10 each). Serum 25-hydroxyvitamin D [25(OH)D], brain BDNF and malondialdehyde levels and activities of acetylcholinesterase (AChE), antioxidant enzymes (glutathione reductase, glutathione peroxidase and superoxide dismutase) and caspase-3 were quantified. Results: Vitamin D supplementation significantly mitigated the observed aging-related reduction in brain BDNF level and activities of AChE and antioxidant enzymes and elevation in malondialdehyde level and caspase-3 activity compared to control groups. Brain BDNF level correlated positively with serum 25(OH) D level and brain AChE activity and negatively with brain malondialdehyde level and caspase-3 activity in supplemented groups. Conclusion: Restoring vitamin D levels may, therefore, represent a useful strategy for healthy brain aging. Augmenting brain BDNF seems to be a key mechanism through which vitamin D counteracts age-related brain dysfunction.

Interferon-beta, but not Glatiramer Acetate treatment induces gender-specific increase in BDNF serum levels in relapsing-remitting multiple sclerosis female patients

Neuroprotection is considered a major therapeutic target in Multiple Sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system (CNS). Accordingly, current disease modifying drugs (DMDs) for MS have been revaluated for their ability to stimulate production of neurotrophic factors that may provide support to neural cells against neurodegeneration. Brain-derived neurotrophic factor (BDNF) is considered the best candidate for such neuroprotective effects in MS. In the present study, we explored a potential effects of Glatiramer Acetate (GA), and Interferon-beta (IFN-b), the first two available treatments of MS, on circulating levels of BDNF considering the different BDNF forms. Using ELISA assays, we quantified mature and total BDNF in the serum of 20 relapsing-remitting MS (RR-MS) patients treated with GA and 31 with INF-beta compared with 20 age-matched RR-MS patients without any DMD. Mature BDNF but not total BDNF was significantly increased by treatment with IFN-b in female patients only, while GA had no effect. These results support a gender-specific role of BDNF in the treatment of RR-MS with INF-b. Of note, the present study was carried out with standardized ELISA assays which are commercially available and, prospectively, might be routinely used in the common clinical practice to monitor the individual response to the therapy with IFN-b.

High-intensity interval training prevents cognitive-motor impairment and serum BDNF level reduction in parkinson mice model

Parkinson’s disease (PD) is a neurodegenerative disease characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra pars compact (SNpc). Previous studies have shown that cognitive deficits and motor impairment symptoms seen in PD and that physical exercise may exert beneficial effects on PD. In most cases, brain-derived neurotrophic factor (BDNF) is involved in such effects. However, little is known on the role of BDNF in exercise, especially high-intensity interval training (HIIT)-related effects on PD. The aim of this study was to investigate the effects of 6 weeks HIIT against experimentally reserpine (RES)-induced PD in male mice, by analyzing the motor coordination, learning and serum BDNF level. Male mice received 20 (s.c) injections of 0.1 mg/kg RES or vehicle, every other day. Rotarod and spontaneous alternation tests were used for measurement of motor coordination and short-term memory, respectively, and serum levels of BDNF were also measured using the ELISA technique. All behavioral tests were performed 48 h after the RES injection. RES injection caused a significant motor coordination and cognitive deficits (p < 0.05) and these effects were reversed in mice after receiving exercise protocol. HIIT improved the motor coordination and cognitive performance against RES administration (p < 0.05). Also, serum BDNF level was decreased in mice RES-induced PD (p < 0.05) and HIIT restored this to control levels (p < 0.05). Taken together, our results suggest that HIIT shows a protective effect in a mice model of PD and may repair motor coordination and cognitive dysfunctions in PD due to increased serum levels of BDNF.

Uremic pruritus and serum brain-derived neurotrophic factor in diabetic and non-diabetic haemodialysis patients.

IntroductionEven though uremic pruritus (UP) is very troublesome for haemodialysis (HD) patients, its underlying mechanism is not fully understood.AimDue to the possible role of brain-derived neurotrophic factor (BDNF) and its higher serum concentration in haemodialysis diabetic patients compared to non-diabetic ones, this study is aimed to evaluate its association with UP among diabetic and non-diabetic patients on maintenance HD.Material and methodsA total of 94 patients were enrolled into the study. A visual analogue scale (VAS) was used to assess pruritus.ResultsNo differences were found between the observed study groups in terms of BDNF serum concentration, other biochemical markers, sleep disturbances, or pruritus presentation.ConclusionsBDNF serum concentration was not found to be associated with UP among HD patients, however further studies are worth performing on a larger group of individuals.

The role of brain-derived neurotrophic factor (BDNF) in cognitive functions

Nerve growth factor (NGF) was uncovered in near beginning the 1950s which had a growth effect on sympathetic and sensory neurons. In the dorsal root neuron ganglion, the second member of a group of neurotrophic factors widely known as the brain-derived neurotrophic factor (BDNF) appeared. Like other members of the neurotrophin group, such as neurotrophin 3 (NT-3) and NT-4/5, it is explained to have trophic effects on peripheral and central neurons. Since BDNF purification in 1982 evidence of its involvement in development, physiology, and brain pathology demonstrated. BNDF is significant within the molecular mechanism of synapse plasticity regarding neuronal growth and cell survival. The initial step associated with the central nervous system depends on its adaption of synapse transmission, especially in the hippocampus and neocortex. Pathological intensities of the BDNF relationship and synapse plasticity affect sort of situations such as epilepsy and chronic pain sensitization, where BDNF applications can affect therapy in neurodegenerative diseases and neuropsychiatric diseases. BDNF plays a pivotal role in cognitive processes, affecting the advancement and brain structures’ motion. Predominantly in the hippocampus and prefrontal cortex, by modulating synaptic neurotransmission, it changes the plasticity and proliferation of neurons through regulation of neuronal migration processes such as differentiation, perseveration, neuronal modification and replacement of synaptic structures. BDNF also affects the development of dopaminergic, serotonergic, cholinergic and GABAergic. BDNF further causes rapid postsynaptic reactions in ion channels and N-Methyl D-Aspartate (NMDA) receptors. BDNF as a vital component in the normal functioning of the brain is one of the neurotrophins that contributes to the development, maintenance of function and healthy neuron cells and cynical plasticity.

Abstract 4854: A translational multiplexed hypothesis generating study on circulating cytokines in patients with cancer cachexia

Abstract Cancer cachexia is a frequent pathophysiological state associated to terminal stage cancer patients, characterized by a significant reduction in body weight and resistant to nutritional interventions. It is an unmet medical need, and its underlying mechanisms are not completely understood. Objectives: To measure multiple soluble cytokines in patients with cachexia, to develop new hypotheses on pathways and/or eventual therapeutic targets. Methods: This is part of a pilot, observational, cross-sectional, case-control, IRB-reviewed translational research in cancer patients with/without cachexia. Anthropometric, clinical and biochemical data from consenting eligible cancer patients were collected. Blood samples were collected from all the participants, and plasma was separated and immediately stored at -20°C until analysis. For this substudy, human 63-plex kits were purchased from eBiosciences and used according to the manufacturer's recommendations. Plates were read using a Luminex 200 instrument, and the assay was performed in the Human Immune Monitoring Center at Stanford University (CA, USA). Data were analyzed by univariate and multivariate methods, using error adjustments for multiple testings (False Discovery Rate, FDR). A total of 15 subjects were included in this study, 8 cachectic and 7 non-cachectic patients. Median age in cachectic group was 61.5 (36-81) years versus 63.9 (48-80) in non-cachectic group. The respective relative weight loss within the prior 3 months was 17.6% and 1.0%. Clinical, analytical and metabolomics from these patients have been reported elsewhere (doi: 10.1002/jcsm.12270). Of the 63 cytokines tested in our panel, 18 have been selected for fold-change (FC) analysis: for 12, their log2(FC)&amp;gt;1 (IL1RA, ENA78, IL8, GROA, IL23, MCP1, BDNF, PDGFB, IL18, IL21, RESISTIN, IL6), being the FC &amp;gt; 10x for IL1RA, ENA78, IL8, GROA and IL23. For the remaining 6, their log2(FC) &amp;lt; -1 (LEPTIN, GMCSF, IL12P40, IL1B, CD40L, IL5). The cytokines selected for their FDR were: LEPTIN, LIF, GMCSF, RESISTIN, TNFA, IL1B, IL12P40, IL4, IL12p70, BDNF, IL2, IL5, IL23, IL17A and IL13. We integrated these results with prior metabolomics research and performed pathway analyses that enabled us to identify a significant enrichment in several pathways related with infections, immune response, inflammation, energy homeostasis and cancer. This study, despite the size constraints, is able to capture known players in cancer cachexia (leptin, IL6, IL1). We show a potential role for BDNF (brain derived neurotrophic factor), which and has been described as a master coordinator of the physiological mechanisms that regulate food intake and energy expenditure, and identified as a player in murine models for cancer cachexia. Results from this study will be integrated with data from additional research in the same patients (clinical, analytical, metabolomics and proteomics). Citation Format: Mª Teresa Agullo-Ortuño, Virginia Pardo-Marques, Elena Prieto-Garcia, C. Vanesa Diaz-Garcia, Irene Otero, Jose A. Lopez-Martin. A translational multiplexed hypothesis generating study on circulating cytokines in patients with cancer cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4854.

Elevated plasma BDNF levels are correlated with NK cell activation in patients with traumatic spinal cord injury

BackgroundThe precise role of innate immune responses in the early stage of traumatic spinal cord injury (SCI), especially those mediated by natural killer (NK) cells, is poorly understood. MethodsThe frequency and phenotype of NK cells from traumatic SCI patients and healthy controls were assessed by flow cytometry. ELISA assay was used to detect the production of a series of cytokines, neurotrophins, and neurohormones in plasma samples. In vitro cell culture was performed to observe brain-derived neurotrophic factor (BDNF)-induced NK cell activation. ResultsA significant increase in the NK cell frequency and the presence of NK cells with the activated phenotype was observed, as reflected by the enhanced expression of CD69, HLA-DR, NKG2D, and NKp30 on the NK cells, in traumatic SCI patients within 24 h of injury, compared to case for the healthy controls. Meanwhile, a higher level of BDNF, a member of the neurotrophin family, was observed in the plasma samples of the SCI patients; the elevated level of BDNF was strongly and positively correlated with the percentage of NK cells during the early stage of traumatic SCI. Furthermore, the expression of CD69 and NKp30 on the NK cells increased following stimulation with BDNF for 24 h in vitro, which is consistent with the in vivo observation in SCI patients. ConclusionCollectively, our findings demonstrate the activation of NK cells within 24 h after traumatic SCI, and reveal a novel role of BDNF in regulating NK cell activation.

The effect of interferon-β therapy on brain-derived neurotrophic factor serum concentration in relapsing— remitting multiple sclerosis: a randomized clinical trial

Introduction: Beta interferon (IFN-β) is known as the first-line therapy in relapsing-remitting multiple sclerosis (RRMS). Recent studies have shown different effects of IFN-β on brain-derived neurotrophic factor (BDNF) serum levels. Given the known role of BDNF in the restoration and conservation of the nervous system, this study was designed to investigate the possible effect of this drug through stimulating BDNF production. Objectives: Impressible treatments for progressive multiple sclerosis (MS) are still being sought. Individual response to existing treatments for MS varies significantly among patients while the risk of serious adverse events remains an issue, especially for the novel drugs. Patients and Methods: In this clinical trial, 96 patients newly diagnosed with RRMS were studied within three months, in 3 groups of 32 subjects. Each group received one of the foregoing drugs (Avonex, Rebif and Betaferon). BDNF levels were compared between different groups at the end. Results: BDNF serum concentration in all groups was significantly different (P&lt;0.001) compared to baseline after 3 months. And comparison between groups showed a significant difference between the groups receiving Betaferon (IFN-β1b) (P=0.001) and Rebif (P=0.002) compared to the other groups. Avonex compared with either control or Betaferon (IFN-β1b) and Rebif groups showed no significant difference. Also the correlation between the mean changes in expanded disability status scale (EDSS) and BDNF was not observed (r = -0.189, P=0.065). Conclusions: Significant difference in BDNF levels were observed between groups.

Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice.

The volatile anesthetic isoflurane is suggested to produce a rapid and robust antidepressive effect in preliminary clinical trials. Recently, isoflurane was found to activate the tropomyosin receptor kinase B (TrkB) signaling which is the underlying mechanism of the rapid antidepressant ketamine. Our study investigated the effect of isoflurane anesthesia on chronic unpredictable mild stressed (CUMS) model in mice and verified the role of brain-derived neurotrophic factor (BDNF)/TrkB/ the mammalian target of rapamycin (mTOR) signaling in the antidepressant effect of isoflurane. We employed the CUMS model of depression to assess the rapid antidepressant effect of isoflurane by the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). The protein expression of BDNF and TrkB/protein kinase B (PKB or Akt)/mTOR was determined through Western blot. The dendritic spine density in the hippocampus and medial prefrontal cortex (PFC) was measured by the Golgi staining. A brief burst-suppressing isoflurane anesthesia rapidly reversed the behavioral deficits caused by CUMS procedure, normalized the expression of BDNF and further activated the TrkB signaling pathway in CUMS-induced stressed mice in both prefrontal cortex (PFC) and hippocampus (HC). All of those behavioral and proteomic effects were blocked by K252a, a selective receptor inhibitor of TrkB. Isoflurane significantly promoted the formation of dendritic spines in both medial prefrontal cortex (mPFC), CA1, CA3, and DG of the hippocampus. Our study indicates that isoflurane exerts a rapid antidepressant-like effect in CUMS depression animal model, and the activation of BDNF/TrkB signaling pathway plays an indispensable role in the biological and behavioral antidepressant effects of isoflurane. A single exposure to isoflurane could repair synaptic damage caused by chronic stimulation.

The Low Molecular Weight Brain-derived Neurotrophic Factor Mimetics with Antidepressant-like Activity.

The search for new highly-effective, fast-acting antidepressant drugs is extremely relevant. Brain derived neurotrophic factor (BDNF) and signaling through its tropomyosin-related tyrosine kinase B (TrkB) receptor, represents one of the most promising therapeutic targets for treating depression. BDNF is a key regulator of neuroplasticity in the hippocampus and the prefrontal cortex, the dysfunction of which is considered to be the main pathophysiological hallmark of this disorder. BDNF itself has no favorable drug-like properties due to poor pharmacokinetics and possible adverse effects. The design of small, proteolytically stable BDNF mimetics might provide a useful approach for the development of therapeutic agents. Two small molecule BDNF mimetics with antidepressant-like activity have been reported, 7,8-dihydroxyflavone and the dimeric dipeptide mimetic of BDNF loop 4, GSB-106. The article reflects on the current literature on the role of BDNF as a promising therapeutic target in the treatment of depression and on the current advances in the development of small molecules on the base of this neurotrophin as potential antidepressants.

The Role of BDNF in the Neuroimmune Axis Regulation of Mood Disorders.

The neuroimmune system plays a crucial role in the regulation of mood disorders. Moreover, recent studies show that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is a key regulator in the neuroimmune axis. However, the potential mechanism of BDNF action in the neuroimmune axis' regulation of mood disorders remains unclear. Therefore, in this review, we focus on the recent progress of BDNF in influencing mood disorders, by participating in alterations of the neuroimmune axis. This may provide evidence for future studies in this field.

The Impact of Physical Exercise on Brain-Derived Neurotrophic Factor (BDNF) Level in Elderly Population

BACKGROUND:Memory function disorder is a major health problem in geriatric patients. Physical exercise has the potency to decrease the incidence of many degenerative and chronic health problem, related to cognitive deterioration (dementia).AIM:This research aimed to observe the effect of physical exercise in various doses and duration on memory function by analysing the role of Brain-Derived Neurotrophic Factor (BDNF) as a regulatory protein affected by exercise.METHODS:This was an analytical observational study with a cohort design. Thirty participants were included in each group, classified as exercise and non-exercise group. The exercise was in the form of jogging for at least fifteen minutes every day. The observation was done for sixty days. Cognitive function assessment was done by using the Mini-Mental State Examination (MMSE) questionnaire. Meanwhile, the BDNF level was assessed by ELISA. Statistical analysis was done using Independent T-test.RESULTS:Exercise group showed better MMSE score (28.56 ± 1.76), and a higher concentration of BDNF (235.34 ± 12.56 pg/mL), both were statistically significant.CONCLUSION:Physical exercise was able to maintain geriatric cognitive function performance by BDNF protein regulation.

BDNF Controls Bidirectional Endocannabinoid Plasticity at Corticostriatal Synapses.

The dorsal striatum exhibits bidirectional corticostriatal synaptic plasticity, NMDAR and endocannabinoids (eCB) mediated, necessary for the encoding of procedural learning. Therefore, characterizing factors controlling corticostriatal plasticity is of crucial importance. Brain-derived neurotrophic factor (BDNF) and its receptor, the tropomyosine receptor kinase-B (TrkB), shape striatal functions, and their dysfunction deeply affects basal ganglia. BDNF/TrkB signaling controls NMDAR plasticity in various brain structures including the striatum. However, despite cross-talk between BDNF and eCBs, the role of BDNF in eCB plasticity remains unknown. Here, we show that BDNF/TrkB signaling promotes eCB-plasticity (LTD and LTP) induced by rate-based (low-frequency stimulation) or spike-timing-based (spike-timing-dependent plasticity, STDP) paradigm in striatum. We show that TrkB activation is required for the expression and the scaling of both eCB-LTD and eCB-LTP. Using 2-photon imaging of dendritic spines combined with patch-clamp recordings, we show that TrkB activation prolongs intracellular calcium transients, thus increasing eCB synthesis and release. We provide a mathematical model for the dynamics of the signaling pathways involved in corticostriatal plasticity. Finally, we show that TrkB activation enlarges the domain of expression of eCB-STDP. Our results reveal a novel role for BDNF/TrkB signaling in governing eCB-plasticity expression in striatum and thus the engram of procedural learning.