Effect of Exercise on Brain-Derived Neurotrophic Factor in Stroke Survivors: A Systematic Review and Meta-Analysis.

BACKGROUND: BDNF (brain-derived neurotrophic factor) is a biomarker of neuroplasticity linked with better functional outcomes after stroke. Early evidence suggests that increased concentrations after exercise may be possible for people with stroke, however it is unclear how exercise parameters influence BDNF concentration. METHODS: This systematic review and meta-analysis searched 7 electronic databases. Experimental or observational studies measuring changes in BDNF concentration after exercise in people poststroke were included. Data were extracted including characteristics of the study, participants, interventions, and outcomes. Several fixed and random effects meta-analyses were completed. RESULTS: Seventeen studies including a total of 687 participants met the eligibility criteria (6 randomized trials). Significant improvements were observed in BDNF concentration following a single session (mean difference, 2.49 ng/mL; [95% CI, 1.10-3.88]) and program of high intensity aerobic exercise (mean difference, 3.42 ng/mL; [95% CI, 1.92-4.92]). CONCLUSIONS: High intensity aerobic exercise can increase circulating BDNF concentrations, which may contribute to increased neuroplasticity. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021251083.

Hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness and distress in chronic tinnitus.

The role of stress and its neuroendocrine mediators in tinnitus is unclear. In this study, we measure cortisol as an indicator of hypothalamus-pituitary-adrenal (HPA) axis alterations and brain-derived neurotrophic factor (BDNF) as a marker of adaptive neuroplasticity in hair of chronic tinnitus patients to investigate relationships with tinnitus-related and psychological factors. Cross-sectional data from chronic tinnitus inpatients were analyzed. Data collection included hair sampling, pure tone audiometry, tinnitus pitch and loudness matching, and psychometric questionnaires. Elastic net regressions with n-fold cross-validation were performed for cortisol (N = 91) and BDNF (N = 87). For hair-cortisol (R2 = 0.10), the strongest effects were sampling in autumn and body-mass index (BMI) (positive), followed by tinnitus loudness (positive) and smoking (negative). For hair-BDNF (R2 = 0.28), the strongest effects were hearing aid use, shift work (positive), and tinnitus loudness (negative), followed by smoking, tinnitus-related distress (Tinnitus Questionnaire), number of experienced traumatic events (negative), and physical health-related quality of life (Short Form-12 Health Survey) (positive). These findings suggest that in chronic tinnitus patients, higher perceived tinnitus loudness is associated with higher hair-cortisol and lower hair-BDNF, and higher tinnitus-related distress with lower hair-BDNF. Regarding hair-BDNF, traumatic experiences appear to have additional stress-related effects, whereas hearing aid use and high physical health-related quality of life appear beneficial. Implications include the potential use of hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness or distress and the need for intensive future research into chronic stress-related HPA axis and neuroplasticity alterations in chronic tinnitus.

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

Purpose: 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 cytokine and neurotrophic factors in nicotine addiction in the conditioned place preference paradigm.

The mechanisms involved in the maintenance of cigarette smoking and nicotine reward remain unclear. Immune response might play an important role in this context. Nicotine may induce both central and systemic inflammatory responses as well as changes in the regulation of brain-derived neurotrophic factor (BDNF). The conditioned place preference (CPP) is a method used for the evaluation of nicotine-induced reward, reproducing nicotine-seeking behavior in humans. So far, there are no studies investigating the relationship between neuroinflammation and nicotine-induced CPP. This study aimed to evaluate the levels of inflammatory mediators and neurotrophic factors in key areas of the central nervous system (CNS) of mice subject to nicotine-induced CPP. CPP was induced with an intraperitoneal administration of 0.5 mg/kg of nicotine in male Swiss mice, using an unbiased protocol. Control group received vehicle by the same route. The levels of cytokines, chemokines, and neurotrophic factors were measured using Enzyme-Linked Immunosorbent Assay (ELISA) in the brain after CPP test. As expected, nicotine induced place preference behavior. In parallel, we observed increased peripheral levels of IL-6 and IL-10 alongside increased hippocampal levels of NGF but decreased GDNF in mice treated with nicotine compared to controls. In the striatum, nicotine promoted decrease of IL-1ß, IL-10 and GDNF levels, while the levels of all the mediators were similar between groups in the pre-frontal cortex. Our results provide evidence on the role of cytokines and neurotrophic factors in nicotine-induced CPP in mice.

Maternal high-fat diet increases anhedonic behavior and modulates hippocampal Mash1 and BDNF expression in adult offspring.

BACKGROUND: The consumption of a high-fat diet (HFD) during pregnancy and perinatal periods can lead to long-term effects in the offspring central nervous system, affecting pathways related to neurogenesis and behavior, and increasing predispositions to depressive and anxiety-like behaviors. Thus, this study aimed to investigate the effects of a maternal HFD on the hippocampi of adult offspring and behaviors related to anxiety and depression. METHODS: The protein and mRNA expression of the brain-derived neurotrophic factor (BDNF), Mash1, Notch1, Hes5, serotonin transporter (SERT), 5-HT1A serotonergic receptor (5-HT1A), tryptophan hydroxylase 2 (TPH2, key enzyme of serotonin synthesis), JNK and pJNK were analyzed in the hippocampi of male Swiss mice. Hippocampal serotonin levels were measured using ELISA. The lipid peroxidation, total oxidant status, total antioxidant status, and GSH/GSSG were evaluated as oxidative stress measures. For the behavioral analysis, the open field, elevated plus maze, and sucrose preference tests were used. RESULTS: Maternal HFD led to increased body weight in dams and their offspring, as well as altered body composition and LDL levels in the offspring. There were no alterations in oxidative stress or JNK phosphorylation. Hippocampal Mash1 and BDNF expression were altered in HFD offspring. The HFD offspring exhibited anhedonic behavior. CONCLUSION: These findings suggest that maternal HFD leads to long-term alterations in the offspring's neurotrophic systems, impairing their behavior.

Functional and structural alternations in the choroid plexus upon methamphetamine exposure.

Choroid plexus (CP) is the principal source of cerebrospinal fluid. CP can produce and release a wide range of materials including growth factors, neurotrophic factors, etc. all of which play an important role in the maintenance and proper functioning of the brain. Methamphetamine (METH) is a CNS neurostimulant that causes brain dysfunction. Herein, we investigated the potential effects of METH exposure on CP structure and function. Stereological analysis revealed a significant alteration in CP volume, epithelial cells and capillary number upon METH treatment. Electron microscopy exhibited changes in ultrastructure. Moreover, the upregulation of neurotrophic factors such as BDNF and VEGF as well as autophagy and apoptosis gene following METH administration were observed. We also identified several signaling cascades related to autophagy. In conclusion, gene expression changes coupled with structural alterations of the CP in response to METH suggested METH-induced autophagy in CP.

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

BACKGROUND: There 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. METHODS: We 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. RESULTS: BDNF 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. CONCLUSIONS: Our 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.

High irisin and low BDNF levels in aqueous humor of high myopia.

BACKGROUND: The pathogenesis of myopia remains unclear. Both genetic and environmental factors play a role in the disease progression. Reasons including reduced physical activity (PA) and low-grade intraocular inflammation may be involved in the development of myopia. OBJECTIVES: To analyze the levels of irisin, brain-derived neurotrophic factor (BDNF) and other intraocular cytokines in aqueous humor of high myopia patients, and to evaluate the roles of PA and inflammation in developing myopia. MATERIAL AND METHODS: We collected aqueous humor samples from patients with axial length (AL) over 26 mm (n = 35) or shorter than 25 mm (n = 38) during cataract extraction surgery. Samples were assayed using the enzyme-linked immunosorbent assay (ELISA) kit for irisin and a multiplex immunoassay kit for BDNF, interleukin (IL)-6, IL-8 and IL-10, and tumor necrosis factor alpha (TNF-α). RESULTS: Irisin levels in the aqueous samples of the highly myopic eyes were significantly higher than in the control group (p = 0.027). The BDNF levels of the highly myopic group were significantly lower than in the control group (p = 0.043). Median level of leukemia inhibitory factor (LIF) for highly myopic group (2.035 pg/mL) was statistically significantly higher than in the control group (0.750 pg/mL) (U = 210.5, Z = -4.495, p < 0.001). Interleukin 1 receptor antagonist (IL-1ra) level in the aqueous samples of the highly myopic group was significantly lower than in the shorter AL group (p = 0.049). Interleukin 6, IL-8 and IL-10 levels were not significantly different between the 2 groups (p = 0.501, p = 0.059 and p = 0.192, respectively). Tumor necrosis factor α levels could only be detected in 30 samples and median levels in the 2 groups were not statistically significantly different (U = 99, Z = -0.482, p = 0.650). No correlation was found between IL-6, IL-8, IL-10 and TNF-α, and the AL (p > 0.05). Irisin was positively correlated with AL (p = 0.028, r = 0.287). The BDNF was negatively correlated with AL (p = 0.040, r = -0.246). Interleukin 1ra was negatively correlated with AL (p = 0.038, r = -0.276). There was also a correlation between LIF and AL (p < 0.001, r = 0.486). CONCLUSIONS: Higher irisin level in high myopia group opens a new direction to discover the relationship between PA and myopia. The decreased BDNF in high myopia group probably demonstrates the connection between myopia and neurodegenerative disease.

Influence of Previous COVID-19 and Mastitis Infections on the Secretion of Brain-Derived Neurotrophic Factor and Nerve Growth Factor in Human Milk.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) play a critical role in neurodevelopment, where breast milk is a significant dietary source. The impact of previous COVID-19 infection and mastitis on the concentration of BDNF and NGF in human milk was investigated. METHODS: Concentrations of BDNF and NGF were measured via ELISA in human milk samples collected from 12 mothers with a confirmed COVID-19 PCR, 13 mothers with viral symptoms suggestive of COVID-19, and 22 unexposed mothers (pre-pandemic Ctl-2018). These neurotrophins were also determined in 12 mothers with previous mastitis and 18 mothers without mastitis. RESULTS: The NGF concentration in human milk was lower in the COVID-19 PCR and viral symptoms groups than in the unexposed group, but BDNF did not differ significantly. Within the COVID-19 group, BDNF was higher in mothers who reported headaches or loss of smell/taste when compared with mothers without the respective symptom. BDNF was lower in mothers with mastitis than in mothers without mastitis. CONCLUSIONS: Previous COVID-19 and mastitis infections changed differently the secretion of NGF and BDNF in human milk. Whether the changes in NGF and BDNF levels in milk from mothers with infection influence their infant's development remains to be investigated.

Relationship between exclusive breastfeeding and brain-derived neurotrophic factor in children.

OBJECTIVE: A positive relationship between breastfeeding and brain-derived neurotrophic factor (BDNF) in infants has been suggested due to the presence of BDNF in human milk. This study aimed to determine the relationship between exclusive breastfeeding and BDNF serum levels in Spanish schoolchildren. METHODS: A cross-sectional analysis including 202 schoolchildren, aged eight to 11 years, from Cuenca, Spain, was conducted. Information on sociodemographic and anthropometric variables, sexual maturation, birth weight and exclusive breastfeeding ('no exclusive breastfeeding', and exclusive breastfeeding for ≤6 and >6 months), and BDNF serum levels using an ELISA method were obtained. Covariance analyses (ANCOVA) were conducted to examine the relationship between serological BDNF and exclusive breastfeeding after controlling for potential confounders. RESULTS: ANCOVA models showed no significant differences in BDNF levels between children who were exclusively breastfed for more than six months versus those who were not (p > 0.05). No significant differences were observed by age group (eight to nine years versus 10 to 11 years; p > 0.05). Additionally, no clear negative trend in BDNF serum levels according to sexual maturation categories was found (p > 0.05). CONCLUSION: These findings suggest that exclusive breastfeeding does not have a significant positive association on BDNF from eight to 11 years, since children who were exclusively breastfed did not have significantly higher BDNF levels than those who were not exclusively breastfed. Likewise, BDNF levels were not found to be negatively affected by hormonal development. Future research should examine the influence of exclusive breastfeeding on BDNF over the different developmental stages.

The role of pre-pubertal training history on hippocampal neurotrophic factors and glucocorticoid receptor protein levels in adult male rats.

Neurotrophic factors play an integral role in hippocampal plasticity, and interaction with HPA axis components, especially glucocorticoid receptors (GR), can mediate the structural and functional changes. In the present work, we investigated the long-term effects of combined exercise training (CET) and voluntary physical activity in an enriched environment (EE) in the pre-pubertal period on hippocampal neurotrophic factors and GR. For this purpose, a longitudinal study was designed. After three weeks, all rats were kept in the standard cages without any interventions until adulthood. Western blot analysis revealed a significant increase in hippocampal BDNF and VEGF protein levels in both EE and CET groups (P < 0.001), along with an increase in GR protein levels. In addition, EE decreased serum corticosterone levels compared to CET (P < 0.05). Serum insulin-like growth factor-1 (IGF-1) levels did not demonstrate remarkable changes between groups. Training interventions during sensitive developmental periods may produce profound and long-lasting effects on the hippocampus, at least in part by interactive effects of neurotrophic factors cascades and GR.

Neurosteroids and Neurotrophic Factors: What Is Their Promise as Biomarkers for Major Depression and PTSD?

Even though major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are among the most prevalent and incapacitating mental illnesses in the world, their diagnosis still relies solely on the characterization of subjective symptoms (many of which are shared by multiple disorders) self-reported by patients. Thus, the need for objective measures that aid in the detection of and differentiation between psychiatric disorders becomes urgent. In this paper, we explore the potential of neurosteroids and neurotrophic proteins as biomarkers for MDD and PTSD. Circulating levels of the GABAergic neuroactive steroid, allopregnanolone, are diminished in MDD and PTSD patients, which corroborates the finding of depleted neurosteroid levels observed in animal models of these disorders. The neurotrophic protein, brain-derived neurotropic factor (BDNF), is also reduced in the periphery and in the brain of MDD patients and depressed-like animals that express lower neurosteroid levels. Although the role of BDNF in PTSD psychopathology seems less clear and merits more research, we propose a causal link between allopregnanolone levels and BDNF expression that could function as a biomarker axis for the diagnosis of both MDD and PTSD.

tDCS and exercise improve anxiety-like behavior and locomotion in chronic pain rats via modulation of neurotrophins and inflammatory mediators.

Anxiety disorders cause distress and are commonly found to be comorbid with chronic pain. Both are difficult-to-treat conditions for which alternative treatment options are being pursued. This study aimed to evaluate the effects of transcranial direct current stimulation (tDCS), treadmill exercise, or both, on anxiety-like behavior and associated growth factors and inflammatory markers in the hippocampus and sciatic nerve of rats with neuropathic pain. Male Wistar rats (n = 216) were subjected to sham-surgery or sciatic nerve constriction for pain induction. Fourteen days following neuropathic pain establishment, either bimodal tDCS, treadmill exercise, or a combination of both was used for 20 min a day for 8 consecutive days. The elevated plus-maze test was used to assess anxiety-like behavior and locomotor activity during the early (24 h) or late (7 days) phase after the end of treatment. BDNF, TNF-ɑ, and IL-10 levels in the hippocampus, and BDNF, NGF, and IL-10 levels in the sciatic nerve were assessed 48 h or 7 days after the end of treatment. Rats from the pain groups developed an anxiety-like state. Both tDCS and treadmill exercise provided ethological and neurochemical alterations induced by pain in the early and/or late phase, and a modest synergic effect between tDCS and exercise was observed. These results indicate that non-invasive neuromodulatory approaches can attenuate both anxiety-like status and locomotor activity and alter the biochemical profile in the hippocampus and sciatic nerve of rats with neuropathic pain and that combined interventions may be considered as a treatment option.

Memory impairment of chewing-side preference mice is associated with 5-HT-BDNF signal pathway.

Although tooth loss is a known risk factor of cognitive function, whether and how the chewing-side preference (CSP) affects memory impairment still remains unclear. This study evaluates the behavior changes in mice after the loss of teeth on one side and explores the role of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) signal pathway within these changes. To this end, CSP mouse models with either the removal of left unilateral molars (CSP-L) or right unilateral molars (CSP-R) were established. Morris water maze test and passive avoidance test were performed to evaluate the mice's learning and memory capacity in the 4th and 8th weeks. The correlation between CSP and brain function changes was validated with changes in 5-HT and BDNF levels. CSP mice's cognitive function was found to be decreased, along with a significant decline in 5-HT1A level, especially in CSP-R mice. BDNF and TrkB levels in CSP-R mice were also significantly lowered. These findings suggest that CSP results in memory impairment, which is associated with the 5-HT-BDNF signaling pathway.

Mycobacterium vaccae nebulization protects Balb/c mice against bronchial asthma through neural mechanisms.

OBJECTIVES: Bronchial asthma can be effectively controlled but not be cured, its etiology and pathogenesis are still unclear, and there are no effective preventive measures. The key characteristic of asthma is chronic airway inflammation, and recent research has found that airway neurogenic inflammation plays an important role in asthma. We previously found that Mycobacterium vaccae nebulization protects against asthma. Therefore, this objective of this study is to explore the effect of M. vaccae nebulization on asthmatic neural mechanisms. METHODS: A total 18 of female Balb/c mice were randomized into normal, asthma control, and M. vaccae nebulization (Neb.group) groups, and mice in the Neb.group were nebulized with M. vaccae one month before the asthmatic model was established. Then, 1 month later, the mice were sensitized and challenged with ovalbumin. Twenty-four hours after the last challenge, mouse airway responsiveness; pulmonary brain-derived neurotropic factor (BDNF), neurofilament-medium length (NF-M, using NF09 antibody), and acetylcholine expression; and nerve growth factor (NGF) mRNA level were determined. RESULTS: We found that the BDNF, NF09, acetylcholine expression, and NGF mRNA level were decreased in the Neb.group compared with levels in the asthma control group. CONCLUSION: M. vaccae nebulization may protected in Balb/c mice against bronchial asthma through neural mechanisms.

Exposure to human relevant mixtures of halogenated persistent organic pollutants (POPs) alters neurodevelopmental processes in human neural stem cells undergoing differentiation.

Halogenated persistent organic pollutants (POPs) like perfluorinated alkylated substances (PFASs), brominated flame retardants (BFRs), organochlorine pesticides and polychlorinated biphenyls (PCBs) are known to cause cancer, immunotoxicity, neurotoxicity and interfere with reproduction and development. Concerns have been raised about the impact of POPs upon brain development and possibly neurodevelopmental disorders. The developing brain is a particularly vulnerable organ due to dynamic and complex neurodevelopmental processes occurring early in life. However, very few studies have reported on the effects of POP mixtures at human relevant exposures, and their impact on key neurodevelopmental processes using human in vitro test systems. Aiming to reduce this knowledge gap, we exposed mixed neuronal/glial cultures differentiated from neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs) to reconstructed mixtures of 29 different POPs using concentrations comparable to Scandinavian human blood levels. Effects of the POP mixtures on neuronal proliferation, differentiation and synaptogenesis were evaluated using in vitro assays anchored to common key events identified in the existing developmental neurotoxicity (DNT) adverse outcome pathways (AOPs). The present study showed that mixtures of POPs (in particular brominated and chlorinated compounds) at human relevant concentrations increased proliferation of NSCs and decreased synapse number. Based on a mathematical modelling, synaptogenesis and neurite outgrowth seem to be the most sensitive DNT in vitro endpoints. Our results indicate that prenatal exposure to POPs may affect human brain development, potentially contributing to recently observed learning and memory deficits in children.

Evaluation of the Effect of Hypericum triquetrifolium Turra on Memory Impairment Induced by Chronic Psychosocial Stress in Rats: Role of BDNF.

BACKGROUND: Chronic psychosocial stress impairs memory function and leads to a depression-like phenotype induced by a persistent status of oxidative stress. Hypericum perforatum L. (St. John's wort) is widely used to relieve symptoms of anxiety and depression; however, its long-term use is associated with adverse effects. Hypericum triquetrifolium Turra is closely related to H. perforatum. Both plants belong to Hypericaceae family and share many biologically active compounds. Previous work by our group showed that methanolic extracts of H. triquetrifolium have potent antioxidant activity as well as high hypericin content, a component that proved to have stress-relieving and antidepressant effects by other studies. Therefore, we hypothesized that H. triquetrifolium would reduce stress-induced cognitive impairment in a rat model of chronic stress. OBJECTIVE: To determine whether chronic treatment with H. triquetrifolium protects against stress-associated memory deficits and to investigate a possible mechanism. METHODS: The radial arm water maze (RAWM) was used to test learning and memory in rats exposed to daily stress using the resident-intruder paradigm. Stressed and unstressed rats received chronic H. triquetrifolium or vehicle. We also measured levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, cortex and cerebellum. RESULTS: Neither chronic stress nor chronic H. triquetrifolium administration affected performance during acquisition. However, memory tests in the RAWM showed that chronic stress impaired different post-encoding memory stages. H. triquetrifolium prevented this impairment. Furthermore, hippocampal BDNF levels were markedly lower in stressed animals than in unstressed animals, and chronic administration of H triquetrifolium chronic administration protected against this reduction. No significant difference was observed in the effects of chronic stress and/or H. triquetrifolium treatment on BDNF levels in the cerebellum and cortex. CONCLUSION: H. triquetrifolium extract can oppose stress-associated hippocampus-dependent memory deficits in a mechanism that may involve BDNF in the hippocampus.

Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a crucial role in the survival, differentiation, growth, and plasticity of the central nervous system (CNS). Post-traumatic stress disorder (PTSD) is a complex syndrome that affects CNS function. Evidence indicates that changes in peripheral levels of BDNF may interfere with stress. However, the results are mixed. This study investigates whether blood levels of BDNF in patients with post-traumatic stress disorder (PTSD) are different. METHODS: We conducted a systematic search in the major electronic medical databases from inception through September 2019 and identified Observational studies that measured serum levels of BDNF in patients with PTSD compared to controls without PTSD. RESULTS: 20 studies were eligible to be included in the present meta-analysis. Subjects with PTSD (n = 909) showed lower BDNF levels compared to Non-PTSD controls (n = 1679) (SMD = 0.52; 95% confidence interval: 0.18 to 0.85). Subgroup meta-analyses confirmed higher levels of BDNF in patients with PTSD compared to non-PTSD controls in plasma, not serum, and in studies that used sandwich ELISA, not ELISA, for BDNF measurement. Meta-regressions showed no significant effect of age, gender, NOS, and sample size. CONCLUSIONS: PTSD patients had increased serum BDNF levels compared to healthy controls. Our finding of higher BDNF levels in patients with PTSD supports the notion that PTSD is a neuroplastic disorder.

BDNF serum levels and cognitive improvement in drug-naive first episode patients with schizophrenia: A prospective 12-week longitudinal study.

Abnormal brain-derived neurotrophic factor (BDNF) levels are involved in cognitive decline in patients with schizophrenia. The role of atypical antipsychotic risperidone in improving cognitive function remains unclear. The study aimed to investigate the effect of risperidone monotherapy on cognitive impairment in drug-naïve first-episode (DNFE) patients with schizophrenia and whether BDNF levels were correlated to the improvement of cognition. 354 DNFE patients and 152 healthy controls were recruited, and we compared their serum BDNF levels and cognition shown on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). High and low BDNF subgroups were defined by median split. Then, 211 patients were treated with risperidone monotherapy for 12 weeks, and their serum BDNF levels and cognition were measured again after treatment. DNFE patients had poorer cognitive functions and lower BDNF levels compared to controls. Lower BDNF levels were correlated with delayed memory in DNFE patients with high baseline BDNF levels. After 12 weeks of treatment, risperidone significantly improved immediate memory, delayed memory and RBANS total scores and BDNF levels were slightly increased. In patients with low-BDNF, BDNF levels were significantly increased after risperidone treatment, while in patients with high-BDNF, BDNF levels were significantly decreased. In addition, baseline BDNF levels were associated with improvement of delayed memory and were a prognostic factor for the improvement of the delayed memory and RBANS total score in patients with high-BDNF. Our result suggests risperidone treatment can partially improve certain domains of the cognitive impairment and baseline BDNF levels are related to cognitive response to risperidone in DNFE patients with schizophrenia.

Oxytocin Reduces Brain Injury and Maintains Blood-Brain Barrier Integrity After Ischemic Stroke in Mice.

The present study was designed to determine the effect of different doses of oxytocin (OXT) on neuronal injury, spatial memory, blood-brain barrier (BBB) integrity and to explore possible underlying molecular mechanisms in the early stage of stroke in mice. Stroke model was generated by middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion in mice. OXT at doses of 1, 2, 4 and 8 IU/per mouse was administrated intranasally at the beginning of brain ischemia. Brain injury, BBB integrity, and spatial memory were evaluated by standard methods. Changes in the expression of nuclear factor-kappa B (NF-κB), and TUNEL positive cell were detected by immunohistochemistry. The levels of vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4) and brain-derived neurotrophic factor (BDNF) proteins were determined by western blotting and ELISA methods. OXT at doses of 4 and 8 IU/per mouse reduced the infarct size by 42% and 52%, respectively, and improved spatial memory function (p < 0.001). OXT (8 IU/per mouse) significantly reduced brain edema, BBB disruption and upregulated the AQP4 expression (p < 0.001). Finally, OXT significantly diminished the number of apoptotic, NF-κB positive cells and enhanced the expression of BDNF and VEGF proteins in the brain tissue (p < 0.001). These findings provide important evidences that OXT significantly suppresses neuronal damage in the early stage of stroke by inhibiting apoptotic and NF-κB signaling pathway, increasing the expression of VEGF, AQP4 and BDNF proteins and reducing the BBB leakage.