Role Of Brain-derived Neurotrophic Factor Research Articles

Elevated Peripheral Brain-Derived Neurotrophic Factor Level Associated With Decreasing Insulin Secretion May Forecast Memory Dysfunction in Patients With Long-Term Type 2 Diabetes.

BackgroundWith the progressive course of diabetes and the decline in islet function, the cognitive dysfunction of patients aggravated.ObjectiveWe aimed to investigate the roles of brain-derived neurotrophic factor (BDNF) and the Val66Met polymorphism in mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 169 Chinese patients with T2DM were involved and divided into long-term (diabetes duration >10 years) and short-term (diabetes duration ≤10 years) diabetes, and in each group, the patients were separated as MCI and the control. Demographic characteristics, clinical variables, and cognitive performances were assessed. The plasma BDNF level was measured via enzyme-linked immunosorbent assay. The Val66Met polymorphisms were analyzed.ResultsLong-term T2DM have lower 2 h postprandial C-peptide (p < 0.05). The BDNF level was slightly higher in patients with MCI than in the controls in each duration group without statistical significance. The relationship of BDNF to Montreal Cognitive Assessment was not proven either. However, in the long-term diabetes group, BDNF concentration remained as an independent factor of logical memory test (β = −0.27; p < 0.05), and they were negatively correlated (r = −0.267; p = 0.022); BDNF was also negatively correlated with fasting C-peptide (r = −0.260; p = 0.022), 2 h postprandial C-peptide (r = −0.251; p = 0.028), and homeostasis model assessment of insulin resistance (r = −0.312; p = 0.006). In genotypic groups, BDNF Val/Val performed better in logical memory test than Met/Met and Val/Met.ConclusionElevated peripheral BDNF level associated with declined islet function, when combined with its Val66Met polymorphism, may forecast memory dysfunction in patients with long-term T2DM.

Brain-Derived Neurotrophic Factor Suppressed Proinflammatory Cytokines Secretion and Enhanced MicroRNA(miR)-3168 Expression in Macrophages

We investigated the role of brain-derived neurotrophic factor (BDNF) and its signaling pathway in the proinflammatory cytokines production of macrophages. The effects of different concentrations of BDNF on proinflammatory cytokines expression and secretion in U937 cell-differentiated macrophages, and human monocyte-derived macrophages were analyzed using enzyme-linked immunosorbent assay and real-time polymerase chain reaction. The CRISPR-Cas9 system was used to knockout p75 neurotrophin receptor (p75NTR), one of the BDNF receptors. Next-generation sequencing (NGS) was conducted to search for BDNF-regulated microRNA. A very low concentration of BDNF (1 ng/mL) could suppress the secretion of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 in lipopolysaccharide (LPS)-stimulated macrophages but did not change their mRNA expression. BDNF suppressed IL-1β and IL-6 secretion in human monocyte-derived macrophages. In U937 cells, BDNF suppressed the phosphorylation of JNK and c-Jun. The p75NTR knockout strongly suppressed IL-1β, IL-6, and TNF-α secretion in macrophages and LPS-stimulated macrophages. BDNF regulated the expression of miR-3168 with Ras-related protein Rab-11A as its target. In conclusion, BDNF suppressed proinflammatory cytokines secretion in macrophages and inhibited the phosphorylation of JNK. Knockout of p75NTR suppressed proinflammatory cytokines expression and secretion. BDNF upregulated the expression of miR-3168. The inhibition of p75NTR could be a potential strategy to control inflammation.

The role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer's disease.

Alzheimer's disease is a neurodegenerative condition that is potentially mediated by synaptic dysfunction before the onset of cognitive impairments. The disease mostly affects elderly people and there is currently no therapeutic which halts its progression. One therapeutic strategy for Alzheimer's disease is to regenerate lost synapses by targeting mechanisms involved in synaptic plasticity. This strategy has led to promising drug candidates in clinical trials, but further progress needs to be made. An unresolved problem of Alzheimer's disease is to identify the molecular mechanisms that render the aged brain susceptible to synaptic dysfunction. Understanding this susceptibility may identify drug targets which could halt, or even reverse, the disease's progression. Brain derived neurotrophic factor is a neurotrophin expressed in the brain previously implicated in Alzheimer's disease due to its involvement in synaptic plasticity. Low levels of the protein increase susceptibility to the disease and post-mortem studies consistently show reductions in its expression. A desirable therapeutic approach for Alzheimer's disease is to stimulate the expression of brain derived neurotrophic factor and potentially regenerate lost synapses. However, synthesis and secretion of the protein are regulated by complex activity-dependent mechanisms within neurons, which makes this approach challenging. Moreover, the protein is synthesised as a precursor which exerts the opposite effect of its mature form through the neurotrophin receptor p75NTR. This review will evaluate current evidence on how age-related alterations in the synthesis, processing and signalling of brain derived neurotrophic factor may increase the risk of Alzheimer's disease.

Protective effects of melatonin in cisplatin-induced cardiac toxicity: possible role of BDNF-TNF-α signaling pathway.

ABSTRACTPurpose:The present study explored the role of melatonin in cisplatin-induced cardiac injury along with the possible role of brain-derived neurotrophic factor (BDNF) in melatonin-mediated effects.Methods:Wistar rats were administered cisplatin (10 mg/kg), and cardiac injury was assessed by measuring the levels of cardiac troponin (cTnT) and lactate dehydrogenase (LDH-1).The extent of apoptosis was measured by measuring caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic) in hearts. The levels of BDNF, tumour necrosis factor α (TNF-α) and reduced glutathione were measured in heart. Melatonin (5 and 10 mg/kg) was administered for 15 days, and the role of BDNF was identified by co-administering BDNF inhibitor, ANA-12 (0.25 and 0.5 mg/kg).Results:Melatonin attenuated cTnT and LDH-1 levels along with reduction in caspase-3 and increase in Bcl-2. It also increased cisplatin-induced decrease in BDNF, increase in TNF-α and decrease in reduced glutathione levels. Moreover, ANA-12 abolished the cardioprotective effects, anti-inflammatory and antioxidant effects of melatonin suggesting the role of BDNF in melatonin-mediated effects in cisplatin-induced cardiac injury.Conclusions:Melatonin is useful in cisplatin-induced cardiac injury, which may be due to an increase in BDNF, decrease in inflammation and increase in antioxidant activities.

Role of brain-derived neurotrophic factor in coping with the consequences of psychotraumatic events

Background: Psychological trauma may cause noticeable damage to the hippocampus, amygdala, and prefrontal cortex. Brain-derived neurotrophic factor (BDNF) demonstrates neuroprotective properties in relation to organic brain damage caused by ischemia and craniocerebral traumas. To date, no sufficient evidence suggests that BDNF provides the viability of the nervous system in the process of overcoming the negative consequences of psychotraumatic events.&#x0D; Aim: To analyze the relationshipbetween the individual psychological manifestations of the "resilient phenotype" and the BDNF level in the blood serum of individuals who have psychological traumatic experience and demonstrate effective coping.&#x0D; Materials and methods: In 33 respondents (26 women, 7 men; mean age, 26.3 7.46 years) who had psychological traumatic experience in the previous 3 years, the BDNF level (determined by quantitative enzyme-linked immunosorbent assay), personality, and behavioral correlates of psychological resilience were explored (using psychological survey). Correlation and multiple regression analyses were used in the mathematical and statistical processing of empirical data.&#x0D; Results: The BDNF level in the blood serum of individuals with a past psychotraumatic event serves as a predictor of the level of expressiveness of resistance to stress (t=2.093, р=0.045), maladaptive states (t=2.511, р=0.018), manifestations of post-traumatic growth ("Personal Strength", t=2.911, р=0.007; "New Opportunities", t=2.242, р=0.032), and psychological well-being (t=3.106, р=0.004).&#x0D; Conclusion: The practical significance of the study is attributed to the formation of evidence base for clinical psychology, improvement of approaches to diagnostics, and provision of clinical and psychological assistance to those affected by psychotraumatic events.

The Role of Brain-Derived Neurotrophic Factor in Epileptogenesis: an Update.

Epilepsy, which is characterized by spontaneous recurrent seizures, is one of the most common and serious chronic neurological diseases in the world. 30% patients failed to control seizures with multiple anti-seizure epileptic drugs, leading to serious outcomes. The pathogenesis of epilepsy is very complex and remains unclear. Brain-derived neurotrophic factor (BDNF), as a member of the neurotrophic factor family, is considered to play an important role in the survival, growth and differentiation of neurons during the development of the central nervous system. Recent years, a series of studies have reported that BDNF can maintain the function of the nervous system and promotes the regeneration of neurons after injury, which is believed to be closely related to epileptogenesis. However, two controversial views (BDNF inhibits or promotes epileptogenesis) still exist. Thus, this mini-review focuses on updating the new evidence of the role of BDNF in epileptogenesis and discussing the possibility of BDNF as an underlying target for the treatment of epilepsy.

Genetic polymorphisms of BDNF on cognitive functions in drug-naive first episode patients with schizophrenia

Brain-derived neurotrophic factor (BDNF) is reported to be involved in cognitive decline in patients with schizophrenia (SZ). Previous studies have found that cognitive deficits remain stable during the chronic disease phase in SZ, but the findings were inconsistent. The role of BDNF in cognitive deficits at different stage of illness remains unclear. This study aimed to examine the effect of BDNF polymorphisms on cognitive deficits in drug-naïve first-episode (DNFE) patients and chronic patients with SZ. 262 DNFE patients, 844 chronic patients, and 1043 healthy controls were recruited to compare 4 polymorphisms in BDNF gene and cognitive function. We found that there was no significant difference in genotype and allele frequencies between SZ patients and controls. However, they were closely related to cognitive functioning. BDNF rs2030324 polymorphism played a strong role in language performance only in DNFE patients with SZ. The language index of DNFE patients with rs2030324 TT and TC genotypes was worse than that of chronic patients, but there was no significant difference in CC genotypes between DNFE and chronic patients. Rs6265 had no significant effect on cognitive functioning in patients and controls. Our result suggests BDNF gene polymorphisms were related to different domains of cognitive function at the different stage of SZ, especially language in DNFE patients.

Brain-derived neurotrophic factor produced long-term synaptic enhancement in the anterior cingulate cortex of adult mice

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) is one of the diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available about the possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependent manner in the ACC in C57/BL6 mice. The enhancement was long-lasting, and persisted for at least 3 h. In addition to the enhancement, BDNF also recruited inactive synaptic responses in the ACC. Bath application of the tropomyosin receptor kinase B (TrkB) receptor antagonist K252a blocked BDNF-induced enhancement. L-type voltage-gated calcium channels (L-VGCC), metabotropic glutamate receptors (mGluRs), but not NMDA receptors were required for BDNF-produced enhancement. Moreover, calcium-stimulated adenylyl cyclase subtype 1 (AC1) but not AC8 was essential for the enhancement. A selective AC1 inhibitor NB001 completely blocked the enhancement. Furthermore, BDNF-produced enhancement occluded theta burst stimulation (TBS) induced long-term potentiation (LTP), suggesting that they may share similar signaling mechanisms. Finally, the expression of BDNF-induced enhancement depends on postsynaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs) and protein kinase Mζ (PKMζ). Our results demonstrate that cortical BDNF may contribute to synaptic potentiation in the ACC.

Brain-derived neurotrophic factor in autoimmune inflammatory diseases (Review).

Numerous recent studies reported that brain-derived neurotrophic factor (BDNF) also exists in the peripheral blood to regulate the proliferation, differentiation and survival of lymphocytes. Besides the role of BDNF in neuron repair, circulatory BDNF also enhances the proliferation and reduces apoptosis of lymphocytes. Peripheral lymphocytes express both BDNF and its receptors. Increasing evidence has indicated that altered BDNF serum levels significantly affect patients with autoimmune inflammatory diseases and may also be linked to the pathogenesis of diseases. For instance, systemic lupus erythematosus, an autoimmune inflammatory disease involving multiple organs, is frequently linked to altered B lymphocyte function, imbalance of T-cell subpopulations and loss of immune tolerance, which dysregulates the immune regulatory network with excessive secretion of inflammatory cytokines. The present review summarized studies that suggest a potential link between circulatory BDNF and autoimmune inflammatory diseases.

Role of brain-derived neurotrophic factor in shaping the behavioural response to environmental stressors.

Brain-derived neurotrophic factor (BDNF) is an important neurotrophin involved in an integration of the brain activity in physiological and pathological conditions, with formation of a short- and long-term functional and structural neuroplasticity. This process proceeds, with a changeable dynamics, in the subsequent stages of ontogenesis. In addition to many other functions in the central nervous system, BDNF is also involved in shaping a response to stress stimuli in the form of precisely adjusted behavioural reactions involving the limbic system, and the endocrine system with stimulation of the hypothalamic-pituitary-adrenal axis (HPA). Although almost every stressor increases the activity of the HPA, the neuronal response to it can vary substantially. This may be due to involvement of different neurotransmitter pathways, neuromodulators and neurohormones, as well as changes in gene expression. It is widely accepted that BDNF synthesis and secretion are modulated by stress. Furthermore, age is an important factor influencing the BDNF expression in response to different stressors. In this work, we focused on the analysis of the role of mild stressful stimuli, which commonly occur in the natural environment, on changes in BDNF expression at various stages of ontogenetic development. Although, the presented data comes from animal studies, probably similar mechanisms of stress regulation are also present in humans. This comprehensive review shows that the influence of stressors on the BDNF expression depends on many factors, including a type and duration of a stressor, time of neurotrophin detection, animal's resistance to stress, brain area, and genotypic characteristics of an individual. A more detailed understanding of the mechanisms shaping stress reactions, including the role of BDNF, may be of both theoretical and practical importance, allowing designing more effective strategies for preventing and treating stress itself and the stress-related disorders.

A Role of BDNF in the Depression Pathogenesis and a Potential Target as Antidepressant: The Modulator of Stress Sensitivity "Shati/Nat8l-BDNF System" in the Dorsal Striatum.

Depression is one of the most common mental diseases, with increasing numbers of patients globally each year. In addition, approximately 30% of patients with depression are resistant to any treatment and do not show an expected response to first-line antidepressant drugs. Therefore, novel antidepressant agents and strategies are required. Although depression is triggered by post-birth stress, while some individuals show the pathology of depression, others remain resilient. The molecular mechanisms underlying stress sensitivity remain unknown. Brain-derived neurotrophic factor (BDNF) has both pro- and anti-depressant effects, dependent on brain region. Considering the strong region-specific contribution of BDNF to depression pathogenesis, the regulation of BDNF in the whole brain is not a beneficial strategy for the treatment of depression. We reviewed a novel finding of BDNF function in the dorsal striatum, which induces vulnerability to social stress, in addition to recent research progress regarding the brain regional functions of BDNF, including the prefrontal cortex, hippocampus, and nucleus accumbens. Striatal BDNF is regulated by Shati/Nat8l, an N-acetyltransferase through epigenetic regulation. Targeting of Shati/Nat8l would allow BDNF to be striatum-specifically regulated, and the striatal Shati/Nat8l-BDNF pathway could be a promising novel therapeutic agent for the treatment of depression by modulating sensitivity to stress.

Investigation of the Molecular Role of Brain-Derived Neurotrophic Factor in Alzheimer's Disease.

Brain-derived neurotrophic factor (BDNF), or abrineurin, is a member of the neurotrophin family of growth factors that acts on both the central and peripheral nervous systems. BDNF is also well known for its cardinal role in normal neural maturation. It binds to at least two receptors at the cell surface known as tyrosine kinase B (TrkB) and p75NTR. Additional neurotrophins that are anatomically linked with BDNF include neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and nerve growth factor (NGF). It is evident that BDNF levels in patients with Alzheimer's disease (AD) are altered. AD is a progressive disorder and a form of dementia, where the mental function of an elderly person is disrupted. It is associated with a progressive decline in cognitive function, which mainly targets the thinking, memory, and behavior of the person. The degeneration of neurons occurs in the cerebral cortex region of brain. The two major sources responsible for neuronal degeneration are protein fragment amyloid-beta (Aβ), which builds up in the spaces between the nerve cells, known as plaques, disrupting the neuron signaling pathway and leading to dementia, and neurofibrillary tangles (NFTs), which are the twisted fibers of proteins that build up inside the cells. AD is highly prevalent, with recent data indicating nearly 5.8 million Americans aged 65 and older with AD in 2020, and with 80% of patients 75 and older. AD is recognized as the sixth leading cause of death in the USA, and its prevalence is predicted to increase exponentially in the coming years. As AD worsens over time, it becomes increasingly important to understand the exact pathophysiology, biomarkers, and treatment. In this article, we focus primarily on the controversial aspect of BDNF in AD, including its influence on various other proteins and enzymes and the current treatments associated with BDNF, along with future perspectives.

Aerobic Exercise Activates Bdnf/creb Pathway And Enhances Behavior Features In Parkinson’S Disease Mice

Neurotrophic factors are associated with neurological disorders including Parkinson’s disease (PD). However, the role of brain-derived neurotrophic factor (BDNF) and the molecular mechanism of relative signaling mediating neuron homeostasis by exercise in PD are unclear. PURPOSE: The effect of exercise on the behavior of PD mice was analyzed, to observe the expression of neurotrophic factor of BDNF mediated by exercise, and to analyze the regulation of BDNF mediated by ERK1/2-CREB pathway. METHODS: After 8 weeks of training, the final group was as follows: Quiet + Saline group (WT), Exercise + Saline group (WE), Quiet + MPTP group (M), Exercise + MPTP group (ME). Mice in M and ME group were injected with intraperitoneal MPTP once each day for 7 times, mice in WT and WE groups received the same dose of saline intraperitoneal injection at the same time. The PD model was made, and the behavioral test was carried out, as well the molecular features were detected by immunofluorescence and Western blot. RESULTS: (1) In the behavior experiment, for step length M group decreased significantly (P < 0.05), but M group ME was significantly increased (P < 0.05) for rotation time; In open field experiment, the central activity track and total distance of WT group were higher than those of M group (P < 0.05). Although the central activity track and total distance of ME group were higher than that of M group, there was no significant difference (P > 0.05). (2) Tyrosine hydroxylase (TH) activity was detected by immunofluorescence and Western blot. Compared with WT, the expression of TH protein in M group was significantly lower (P < 0.01), while TH protein expression was increased in ME group compared with M group (P < 0.05). (3) Compared with group M, BDNF and TrkB protein expression increased after exercise training (P < 0.05). The protein expression of downstream signal marker ERK (P < 0.01), P-ERK (P < 0.01) and P-CREB (P < 0.05) were also up-regulated. CONCLUSION: Exercise training increases the neurotrophic factor BDNF expression, and activates the BDNF-CREB signaling pathway in central nervous system, in which exercise promotes the motor behavior, and alleviates the pathological features in PD mice. Key words: aerobic exercise; motor features; Tyrosine hydroxylase (TH); Neurotrophic factor BDNF; Parkinson’s disease

Interplay of Val66Met and BDNF methylation: effect on reward learning and cognitive performance in major depression

BackgroundThere is a growing interest in the role of brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). BDNF potentially exhibits opposite effects in the pathways linked to anhedonia and reward learning on the one hand and cognitive performance, on the other hand. However, the epigenetic mechanisms behind this remain unknown. In the present study, we aimed to investigate the interplay of DNA methylation of different BDNF exons and the common Val66Met polymorphism on anhedonia, reward learning and cognitive performance in MDD.MethodsWe recruited 80 depressed patients and 58 age- and gender-matched healthy controls. Participants underwent clinical assessment including neuropsychological testing and a probabilistic reward task to assess reward learning. Val66Met polymorphism and DNA methylation of BDNF promoters I, IV and exon IX were assessed from whole blood derived DNA, using pyrosequencing.ResultsBDNF promoter I methylation was lower in MDD patients (p = 0.042) and was negatively associated with self-reported anhedonia. In depressed patients, both Val66Met polymorphism and DNA methylation of promoter I were significantly associated with reward bias (p < 0.050 and p = 0.040, respectively), without an interaction effect. On the other hand, methylation of exon IX had a negative impact on executive functioning (p = 0.002) and mediated the effect of Val66Met on this outcome in patients with MDD.ConclusionsOur results provide the first evidence of Val66Met susceptibility to differential epigenetic regulation of BDNF exons in reward learning and executive functioning in MDD, which needs to be further explored.

The Effect of IFN-β Treatment on Plasma Levels of BDNF and IL-6 in Relapsing-Remitting Multiple Sclerosis Patients

Background: In recent investigations addressing neurodegenerative diseases, especially multiple sclerosis (MS), the roles of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) have been examined. Methods: Forty-five relapsing-remitting MS (RRMS) patients, including 32 IFN-β-treated and 13 newly identified untreated cases as well as 45 sex- and age-matched healthy controls, were recruited in the study. Plasma levels of BDNF and IL-6 were assessed using the ELISA method. Data were analyzed by SPSS (ver.21). Results: There were significant differences between the case and healthy control groups in terms of the plasma levels of BDNF (p value = 0.044) and IL-6 (p value <0.001). Besides, the treatment with IFN-β had no significant impact on the level of BDNF or IL-6 in RRMS patients as compared to healthy controls (p value = 0.716 and 0.623 for BDNF and IL-6, respectively). Furthermore, the increase in the plasma levels of BDNF and IL-6 indicated a direct correlation in the case group (r = 0.508, p value = 0.008). In detail, following the classification of the case group into 2 subgroups of IFN-β-treated and untreated patients, a direct positive correlation was observed between the plasma levels of BDNF and IL-6 in IFN-β-treated patients (r = 0.495, p value = 0.026). Conclusion: The IFN-β treatment seems not to be effective for upregulating BDNF and IL-6 in RRMS patients.

Elevation of DNA Methylation in the Promoter Regions of the Brain-Derived Neurotrophic Factor Gene is Associated with Heroin Addiction.

To study the potential role of brain-derived neurotrophic factor (BDNF) methylation in heroin addiction, we first detected the methylation level of seven CpG islands that included 106 CpG sites in the promoter regions of BDNF from 120 people addicted to heroin and 113 controls. Methylation quantitative trait locus (mQTL) analysis was then employed to determine the association between the single-nucleotide polymorphism rs6265, a well-known locus shown to be correlated with heroin addiction, and the methylation levels of these CpG sites. Finally, we used the JASPAR database to predict whether transcription factors could bind to these CpG sites. We found that the methylation levels of CpG islands 6 and 7 and the methylation levels of BDNF_45 and BDNF_80 were significantly higher in the heroin addiction group than in the control group. We also found that rs6265 was an mQTL and was associated with the methylation level of BDNF_58. Using the JASPAR database, we found that ALX homeobox 3 (ALX3), achaete-scute family bHLH transcription factor 1 (ASCL1) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) could bind to CpG island 6, and ALX3 could bind to CpG island 7. In summary, we showed that increased DNA methylation in the promoter regions of the BDNF gene was associated with heroin addiction in Han Chinese.

Low BDNF levels in serum are associated with cognitive impairments in medication-naïve patients with current depressive episode in BD II and MDD

ObjectiveThis study aimed to investigate the role of Brain-derived neurotrophic factor (BDNF) in clinical and cognitive outcomes in medication-naïve patients with Bipolar type II disorder (BD II) and Major depressive disorder (MDD). Methods45 outpatients with BD II, 40 outpatients with MDD and 40 healthy controls (HCs) were recruited, and sociodemographic and clinical data were collected. Their BDNF serum levels were measured and analyzed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). ResultsBDNF levels were significantly lower in BD II patients than in MDD patients and HCs (p = 0.001). BD II and MDD patients had similar cognitive performance deficits shown on Attention (p = 0.001), Delayed memory (p = 0.001), and RBANS total score (p = 0.001). BDNF levels were positively associated with Visuospatial / constructional and Stroop color-word in BD II group, and with language in MDD group. The area under the curve (AUC) of the ROC analysis in BD II vs. MDD was 0.664, therefore, BDNF levels could not distinguish BD II from MDD. ConclusionOur study showed the decreased serum BDNF in MDD and BD II patients, suggesting BDNF may be involved in the pathophysiology of MDD and BD II. BDNF and cognitive deficits are both of low efficiency in distinguishing BD II from MDD. Decrease of BDNF may potentially indicate cognitive dysfunction in BD II and MDD patients with a current depressive episode.

Brain-derived neurotrophic factor attenuates cognitive impairment and motor deficits in a mouse model of Parkinson's disease.

BackgroundParkinson's disease (PD) is one of the most common neurodegenerative disorders that seriously impair the life quality and survival of patients. Herein, we aim to investigate the neuroprotective roles of brain‐derived neurotrophic factor (BDNF) in PD mice and reveal the underlying mechanisms. BDNF overexpression was achieved via the injection of adeno‐associated viruses (AAV) with BDNF gene.MethodsPD mouse model was established by 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) treatment. Tests of rotarod, pole, open field, and novel object recognition were conducted to evaluate the motor and cognitive functions of treated mice.ResultsMitochondrial impairment, mitochondrial respiratory chain enzymes, and tyrosine hydroxylase (TH)‐positive dopaminergic neurons were detected to uncover the molecular mechanism. BDNF overexpression attenuated motor deficits and cognitive impairment in MPTP‐induced PD mice. Mechanistically, BDNF mitigated mitochondrial impairment increased the activity of respiratory chain Complex I and Ⅱ+III, and finally alleviated TH‐positive dopaminergic neuron loss in MPTP‐induced PD mice.ConclusionThis study highlights the potential of BDNF as a therapeutic candidate for the treatment of mitochondrial impairment‐associated neurodegenerative diseases.

Effects of enriched environment on depression and anxiety-like behavior induced by early life stress: A comparison between different periods

BackgroundBrain development is a prolonged process and it is sensitive to the environment during critical periods. Stress in early life is believed to increase vulnerability to depression, while enriched environment (EE) has beneficial effects on neural plasticity and depression. In this study, we compared the therapeutic effect of EE during different periods on early life stress-induced depression, and investigated the role of brain-derived neurotrophic factor (BDNF) and protein kinase B (AKT) on the effect of EE. Plasma corticosterone level was also detected to evaluate the reactivity of hypothalamic-pituitary-adrenal axis. MethodsC57BL/6 mice were subjected to a 4-h maternal separation (MS) procedure during postnatal days 2–21. After this separation, the mice were assigned to standard environment groups (SE), EE in the early period groups (3–8 weeks, EEE) and EE in the adult groups (8–13 weeks, EEA). Depression and anxiety behavior were evaluated at 14-weeks of age. The plasma corticosterone was quantified utilizing enzyme-linked immunosorbent assay. Hippocampus BDNF and AKT/p-AKT were detected using Western blotting. ResultsThe results showed that MS increased depression and anxiety level, while EE in both intervention periods alleviated the symptoms of depression and anxiety. The EEE group showed better effects in terms of anhedonia and anxiety than the EEA group. The difference in despair behavior between the EEE and EEA groups was not significant. MS increased plasma corticosterone level, while EE decreased corticosterone level in both intervention periods. EE increased BDNF and p-AKT expression in the hippocampus, with stronger effects in the EEE group. ConclusionEE during the early development period was more effective in alleviating depression and anxiety induced by early life stress. BDNF and AKT may play a significant role in the effect of EE, and further research is needed to explore the detailed neurobiological mechanisms.

Increased telomerase activity in major depressive disorder with melancholic features: Possible role of pro-inflammatory cytokines and the brain-derived neurotrophic factor

The biological mechanisms responsible for depression symptoms are not yet understood. For this reason, it is important to reveal the etiopathogenetic mechanisms in this disease. This study aims to compare the levels of pro-inflammatory cytokines, Brain-Derived Neurotrophic Factor (BDNF), and telomerase activity in patients with major depressive disorder (MDD) and healthy controls. Plasma BDNF, interleukin-6 (IL-6), IL-1beta, and Tumor Necrosis Factor-alpha (TNF-alpha) levels, and telomerase activity were measured in 39 patients with major depression and 39 healthy controls matched with patients in terms of age, gender, and education year. Plasma concentration of BDNF, IL-6 levels, and telomerase activity was significantly different between patients with MDD and healthy controls. Correlation analysis showed a positive trend between plasma BDNF levels and plasma IL-6 levels in patients with MDD with melancholic features. Furthermore, the path analysis results showed that the telomerase activity was indirectly affected by gender, IL-1β, IL-6, BDNF, and BMI, via the severity of depression and anxiety and MDD status as the mediators. Further studies are needed to examine the molecular mechanism of the telomerase activity and the role of BDNF and pro-inflammatory cytokines in the telomerase activation in MDD.