Increased Brain-derived Neurotrophic Factor Levels Research Articles

How BDNF affects working memory in acute sleep deprivation: The mediating role of spontaneous brain activity

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD.

Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis.

Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.

Upregulation Effect of Citrus Species on Brain-Derived Neurotrophic Factor.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays fundamental roles in neuronal survival and synaptic plasticity. Its upregulation in the brain can effectively prevent and treat central nervous system (CNS) diseases, including depression, Alzheimer's disease (AD), and Parkinson's disease (PD). BDNF is synthesized in various peripheral tissues as well as in the brain and can be transported from peripheral circulation into the brain through the blood-brain barrier. Therefore, foods that upregulate BDNF in peripheral tissues may be beneficial in preventing and treating these CNS diseases. Previously, we revealed that treatment with Chinpi (Citrus unshiu peel) and Citrus natsudaidai increased BDNF levels in the human renal adenocarcinoma cell line ACHN. Here, we evaluated the effects of 21 citrus cultivars on BDNF production in ACHN cells by measuring BDNF levels in the cell culture medium. We found that treatment with peels and pulps of 13 citrus varieties increased BDNF levels in ACHN cells. Treatment with Aurantium, Acrumen, and their hybrids citrus varieties showed a potent BDNF-upregulating effect but not with varieties belonging to Limonellus, Citrophorum, and Cephalocitrus. In addition, treatment with some of those Acrumen and its hybrid citrus species resulted in elevated levels of BDNF transcripts in ACHN cells. These results suggest that peels of many citrus cultivars contain ingredients with a potential BDNF-upregulating ability, which may be novel drug seeds for treating depression, AD, and PD. Furthermore, many citrus cultivars could be used as BDNF-upregulating foods.

Effect of smoking on Brain-Derived Neurotrophic Factor (BDNF) blood levels: A systematic review and meta-analysis

BackgroundBrain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that plays a crucial role in neuronal survival and plasticity. Previous studies have suggested that smoking may influence BDNF levels, but the findings have been inconsistent. MethodsA comprehensive search of electronic databases was conducted to identify relevant studies. Inclusion criteria were applied to select studies that investigated the relationship between smoking and blood levels of BDNF. A random-effects model was used to estimate the overall effect size. ResultsA total of 23 studies were included. The meta-analysis revealed a significant association between smoking and increased blood levels of BDNF (standardized mean difference [SMD] = −0.38, 95 % confidence interval [CI] 0.15 to 0.62, p = 0.002). Subgroup analyses based on BDNF source showed a significant increase in plasma-derived BDNF levels (SMD = 1.02, 95 % CI 0.50 to 1.53, p = 0.0001), while no significant difference was observed in serum-derived BDNF levels (SMD = 0.02, 95 % CI -0.19 to 0.22, p = 0.87). The pooled analysis revealed a non-significant difference in blood levels of BDNF between former smokers and non-smokers (random-effects model, SMD = 0.21, 95 % CI -0.04 to 0.46, p = 0.1). ConclusionSmokers exhibited significantly higher plasma levels of BDNF compared to non-smokers. Further research is needed to elucidate the underlying mechanisms and explore the potential therapeutic implications of targeting BDNF in smoking.

Enhanced peripheral levels of BDNF and proBDNF: elucidating neurotrophin dynamics in cocaine use disorder

Brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF, are known to significantly contribute to brain homeostasis, neuroplasticity, and neuronal remodeling. Although these neurotrophins are thought to have opposing roles, both play a critical part in shaping long-lasting behavioral changes following substance use. In this context, our study sought to explore the implications of these neurotrophins in the pathophysiology of cocaine use disorder (CUD). We conducted a case-control study, which included 28 individuals seeking treatment for CUD and 38 matched healthy participants. We measured peripheral neurotrophin concentrations via an enzyme-linked immunosorbent assay. Additionally, all participants were screened for cocaine-associated pathways (e.g., cocaine intake, craving intensity), along with associated psychopathological data. Our findings highlighted an increased concentration of BDNF and proBDNF in CUD individuals when compared to healthy controls (BDNF: 18092.80 ± 6844.62 vs. 11334.42 ± 5061.85 pg/ml, p < 0.001; proBDNF: 87.03 ± 33.23 vs. 55.70 ± 23.26 ng/ml, p < 0.001). We further corroborated the relationship between neurotrophin levels and CUD using a linear regression model. Nevertheless, there was no significant difference in the proBDNF to BDNF ratio between the two groups. Interestingly, our study also demonstrated the influence of factors like usage of psychotropic medications, history of psychiatric hospitalizations, and psychiatric diagnoses on neurotrophin dynamics. In conclusion, our study underscores the significance of neurotrophin fluctuations in CUD. The observed increase in BDNF and proBDNF levels could play a pivotal role in driving craving and relapse risk. Thus, a nuanced understanding of these neurobiological underpinnings in CUD might contribute to the development of more targeted and effective therapeutic strategies.

Simvastatin mitigates vascular cognitive impairment in rat’s hippocampus in lacunar cerebral infarction

Simvastatin is used to treat Alzheimer’s disease with impaired cognitive function through blocking of PI3K/Akt signaling to inhibit survival of new neurons and growth of neurons. This study investigated the potential of simvastatin on vascular cognitive impairment (VCI) caused by lacunar cerebral infarction (LCI) in the hippocampus of rats. After establishment of LCI models, rats were administered with NaOH solution (model group), simvastatin (simvastatin group), and PI3K/Akt pathway inhibitor (inhibitor group), respectively, and 10 healthy rats served as control group. Upon treatment, Y-maze and Morris water maze detected spatial cognition ability of rats; while cleaved caspase-3 staining was used to assess apoptosis in the hippocampus. Western blot analysis detected Akt and ERK1/2 phosphorylation levels and enzyme-linked immuno sorbent assay (ELISA) determined the content of brain-derived neurotrophic factor (BDNF). The Y maze Morris water maze confirmed impairment of long-term memory abilities in the LCI rats from the model group. Treatment with simvastatin significantly improved correct rate of arm alternates in rats and shorted the stage latency in the hidden platform experiment. The number of apoptotic cells increased in the hippocampal DG sub-granular area of rats with LCI, and BDNF level was significantly reduced. Administration of simvastatin suppressed cell apoptosis and increased BDNF level when improving phosphorylation level of Akt and ERK1/2 as well. Cerebral ischemia following LCI affects short and long-term memory, which leads to VCI. Simvastatin increases Akt and ERK1 in PI3K/Akt pathway, and hence up-regulates hippocampal BDNF levels, which promotes the regeneration of rat hippocampal nerve cells to relieve VCI.

Plasma irisin and the brain-derived neurotrophic factor levels in sedentary subjects: effect of 8-weeks lifestyle intervention.

Objectives. Sedentary lifestyle increasingly observed in the population contributes to the incremental incidence of obesity, cardiovascular diseases, mental disorders, type 2 diabetes, hyper-tension, dyslipidemia, and others. Physical inactivity together with an imbalance in caloric intake and expenditure leads to a loss of muscle mass, reduced insulin sensitivity, and accumulation of the visceral fat. Organokines (adipokines, myokines, hepatokines, etc.) serve in the organism for inter-organ communication. However, human studies focused on the exercise-related changes in plasma levels of certain myokines have produced contradictory results. In the present study, we verified a hypothesis that myokine irisin, which is expected to increase in response to physical activity, induces brain-derived neurotrophic factor (BDNF) production and by this way mediates the beneficial effect of exercise on several brain functions. Subjects and Methods. Women (n=27) and men (n=10) aged 44.5±12.0 years, who were sedentary and overweight/obese (men ≥25%, women ≥28% body fat), participated in the study. The effect of an 8-week intensive lifestyle intervention (150 minutes of moderate physical activity per week, diet modification, and reduction of caloric intake) on the selected organokines (irisin, BDNF) in the context of an expected improvement in cardiometabolic status was examined. Results. The 8-week lifestyle intervention resulted in a significant (p<0.05) reduction in body mass index, body fat, blood pressure, insulin resistance, lipid and liver parameters, and irisin levels (p<0.001). However, BDNF increase in the whole group did not reach statistical significance. After the improvement of cardiometabolic parameters, a significant decrease in irisin and increase in BDNF levels were also observed in the subgroup with unsatisfactory (≤5%) body weight reduction. Neither relationship between irisin and BDNF levels, nor effect of age or sex on their levels was observed. Conclusions. We cannot confirm the hypothesis that exercise-induced irisin may increase the BDNF levels, whereas, the organokine levels in the periphery may not completely reflect the processes in the brain compartments. The observed decrease in irisin levels after 8-week intensive lifestyle intervention program, which was in contrary to its supposed mechanisms of action and dynamics, suggests the presence of several yet undiscovered impacts on the secretion of irisin.

Effects of acute and chronic high-intensity interval training on serum irisin, BDNF and apelin levels in male soccer referees

This study was aimed to investigate the effects of acute and chronic High Intensity Interval Training (HIIT) on Irisin, BDNF (brain-derived neurotrophic factor), and Apelin levels. The study included twenty-one male soccer referees. Blood from the participants was collected at the beginning of study (1. first measurement: baseline value). HIIT was conducted and blood was immediately collected (2. second measurement: acute effect). Next, HIIT was carried out for 20 minutes of 4 days a week in bouts of running (75 meters in 20 seconds) and walking (25 meters in 20 seconds). Blood was collected at the end of 12 weeks (3. third measurement: chronic effect). HIIT was performed and blood was again collected (4. fourth measurement: acute effect after the chronic effect). There was a gradual increase in irisin, BDNF, and apelin levels (p &lt; 0.001). The increase for irisin was 2% in the second measurement, 106% in the third, and 111% in the fourth compared to the first measurement. The increase for BDNF was 39% in the second measurement, 116% in the third, and 133% in the fourth. Apelin levels were increased by 11%, 19%and 28%, respectively. These results demonstrated that irisin and BDNF might increase only in response to chronic HIIT (4 times a week) while apelin levels might change with both acute and chronic HIIT in healthy trained referees.

Levels of BDNF and NGF in adolescent rat hippocampus neonatally exposed to methamphetamine along with environmental alterations.

Neurotrophins are proteins included in development and functioning of various processed in mammalian organisms. They are important in early development but as well as during adulthood. Brain - derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been previously linked with many psychiatric disorders such as depression and addiction. Since during postnatal development, brain undergoes various functional and anatomical changes, we included preweaning environment enrichment (EE), since enrichment has been linked with improved function and development of the several brain structure such as hippocampus (HP), in which we monitored these changes. On the other hand, social isolation has been linked with depression and anxiety-like behavior, therefore postweaning social isolation has been added to this model as well and animal were exposed to this condition till adolescence. We examined if all these three factors had impact on BDNF and NGF levels during three phases of adolescence - postnatal days (PDs) 28, 35 and 45. Our results show that EE did not increase BDNF levels neither in control or MA exposed animals and these results are similar for both direct and indirect exposure. On the other side, social separation after weaning did reduce BDNF levels in comparison to standard housing animals but this effect was reversed by direct MA exposure. In terms of NGF, EE environment increased its levels only in indirectly exposed controls and MA animals during late adolescence. On the other hand, social separation increased NGF levels in majority of animals.

Upregulation of brain-derived neurotrophic factor by Shiikuwasha (Citrus depressa Hayata)

BackgroundA reduction in the brain-derived neurotrophic factor (BDNF) level in the brain causes depression, whereas an increase in its level has therapeutic benefits against depression. BDNF is synthesized in various peripheral tissues and transported to the brain via the peripheral circulation across the blood–brain barrier. Therefore, substances that upregulate peripheral BDNF level may be used to prevent and treat depression. Previously, we demonstrated that Citrus unshiu peel (Chinpi) and C. natsudaidai increased BDNF level in a human renal adenocarcinoma cell line ACHN, which has BDNF-producing ability. Here, we evaluated whether Shiikuwasha (C. depressa Hayata), a citrus species cultivated in East Asia, can upregulate BDNF level in ACHN cells.MethodsWe evaluated the effects of test samples on BDNF production by measuring BDNF level in the medium of ACHN cells after a 24 h cultivation in the presence of test samples. The BDNF mRNA level was measured by quantitative reverse transcription-polymerase chain reaction, and the phosphorylation level of cyclic adenosine monophosphate response element-binding protein (CREB), a transcription factor regulating BDNF expression, was determined using Western blotting.ResultsWe found that methanol extracts of Shiikuwasha peel, pulp, and seed increased the BDNF level in the culture medium of ACHN cells. Shiikuwasha peel and pulp extracts also upregulated BDNF mRNA level and phosphorylation of CREB.ConclusionsThese results suggest that Shiikuwasha includes the candidate antidepressant substances with peripheral BDNF-upregulation effect.

D-mannose is a rapid inducer of ACSS2 to trigger rapid and long-lasting antidepressant responses through augmenting BDNF and TPH2 levels

The potentiation of synaptic plasticity and serotonin generation by brain-derived neurotrophic factor (BDNF) and tryptophan hydroxylase 2 (TPH2) is well characterized to facilitate rapid and long-lasting antidepressant actions. Therefore, the identification of the key protein that simultaneously controls both BDNF and TPH2 is important for the treatment of depression. We show here that a lack of acetyl-CoA synthetase short-chain family member 2 (ACSS2) causes impairments in BDNF-dependent synaptic plasticity and tryptophan hydroxylase 2 (TPH2)-mediated serotonin generation, thereby contributing to spontaneous and chronic restraint stress (CRS)-induced depressive-like behavior in mice. Conversely, D-mannose is identified as a rapid ACSS2 inducer and thus mediates rapid and long-lasting antidepressant-like effects. Mechanistically, acute and chronic D-mannose administration inhibits the phosphorylation of EF2 to increase BDNF levels and reverse the reduction of TPH2 histone acetylation and transcription. We reveal that ACSS2 promotes TPH2 histone acetylation and transcription with the requirement of AMPK activation. To elevate nuclear ACSS2 levels, D-mannose can rapidly and persistently activate AMPK via Ca2+-CAMKK2 and the lysosomal AXIN-LKB1 pathway to facilitate its fast-acting and persistent antidepressant responses. Taken together, the results presented here reveal that ACSS2 functions as a novel target to link rapid and persistent antidepressant actions and further suggest that D-mannose is a potential therapeutic agent to resist depression through its augmentation of the ACSS2 dependent BDNF and TPH2 pathways.

Comparative Efficacy of Metformin and Glimepiride in Modulating Pharmacological Network to Increase BDNF Levels and Benefit Type 2 Diabetes-Related Cognitive Impairment.

Cognitive impairment is anotable complication of type 2 diabetes (T2DM), accompanied by reduced brain-derived neurotrophic factor (BDNF) in the brain and blood. Anti-diabetic drugs reduce hyperglycemia, yet their effect on cognitive improvement is unknown. We aimed to investigate the effect of anti-diabetic drugs regulating BDNF in T2DM through computational and case-control study design. We obtained T2DMproteins viatext-mining to construct a T2DMprotein network. From the T2DMnetwork, the metformin and glimepiride interactomes and their crucial shortest-path-stimulating BDNF were identified. Using qRTPCR, the genes encoding the shortest-path proteins were assessed in four groups (untreated-T2DM, metformin-treated, glimepiride-treated, and healthy controls). Finally, ELISA was used to assess serum BDNF levels to validate drug efficacy. As a result of this investigation, aT2DMnetwork was constructed with 3683 text-mined proteins. Then, the T2DMnetwork was explored to generate a metformin and glimepiride interactome that establishes the critical shortest-path for BDNF stimulation. Metformin stimulates BDNF via APP binding to the PRKAB1 receptor. Whereas, glimepiride increases BDNF by binding to KCNJ11 via AP2M1 and ESR1 proteins. Both drug shortest-path encoding genes differed significantly between the groups. Unlike metformin, BDNF gene and protein expression rise significantly with glimepiride. Overall, glimepiride can effectively increase BDNF, which could benefit T2DM patients with cognitive deterioration.

Increased peripheral of brain-derived neurotrophic factor levels in phenylketonuric patients treated with l-carnitine

Phenylketonuria (PKU) is the most common inherited metabolic disorders caused by severe deficiency or absence of phenylalanine hydroxylase activity that converts phenylalanine (Phe) to tyrosine. PKU patients were treated with a Phe restricted diet supplemented with a special formula containing l-carnitine (L-car), well-known antioxidant compound. The lack of treatment can cause neurological and cognitive impairment, as severe mental retardation, neuronal cell loss and synaptic density reduction. Although Phe has been widely demonstrated to be involved in PKU neurotoxicity, the mechanisms responsible for the CNS injury are still not fully known. In this work, we evaluated markers of neurodegeneration, namely BDNF (brain-derived neurotrophic factor), PAI-1 total (Plasminogen activator inhibitor-1 total), Cathepsin D, PDGF AB/BB (platelet-derived growth factor), and NCAM (neuronal adhesion molecule) in plasma of PKU patients at early and late diagnosis and under treatment. We found decreased Phe levels and increased L-car concentrations in PKU patients treated with L-car compared to the other groups, indicating that the proposed treatment was effective. Furthermore, we found increased BDNF levels in the patients under treatment compared to patients at early diagnosis, and a positive correlation between BDNF and L-car and a negative correlation between BDNF and Phe. Our results may indicate that in PKU patients treated with L-car there is an attempt to adjust neuronal plasticity and recover the damage suffered, reflecting a compensatory response to brain injury.

Effect of alcohol on Brain-Derived Neurotrophic Factor (BDNF) blood levels: a systematic review and meta-analysis

Brain-Derived Neurotrophic Factor (BDNF) is a vital protein involved in neuronal development, survival, and plasticity. Alcohol consumption has been implicated in various neurocognitive deficits and neurodegenerative disorders. However, the impact of alcohol on BDNF blood levels remains unclear. This systematic review and meta-analysis aimed to investigate the effect of alcohol consumption on BDNF blood levels. A comprehensive search of electronic databases was conducted to identify relevant studies. Eligible studies were selected based on predefined inclusion criteria. Data extraction was performed, and methodological quality was assessed using appropriate tools. A meta-analysis was conducted to estimate the overall effect size of alcohol consumption on BDNF levels. A total of 25 studies met the inclusion criteria and were included in the final analysis. Alcohol use and BDNF blood levels were significantly correlated, according to the meta-analysis (p = 0.008). Overall, it was discovered that drinking alcohol significantly decreased BDNF levels (SMD: − 0.39; 95% CI: − 0.68 to − 0.10; I2: 93%). There was a non-significant trend suggesting that alcohol withdrawal might increase BDNF levels, with an SMD of 0.26 (95% CI: − 0.09 to 0.62; I2: 86%; p = 0.14). Subgroup analysis based on the source of BDNF demonstrated significant differences between the subgroups (p = 0.0008). No significant publication bias was observed. This study showed that alcohol consumption is associated with a significant decrease in BDNF blood levels. The findings suggest a negative impact of alcohol on BDNF levels regardless of alcohol dosage. Further studies are needed to strengthen the evidence and elucidate the underlying mechanisms.

Effects of Regular Exercise and Intermittent Fasting on Neurotransmitters, Inflammation, Oxidative Stress, and Brain-Derived Neurotrophic Factor in Cortex of Ovariectomized Rats.

A collection of metabolic disorders and neurodegenerative diseases linked to oxidative stress and neuroinflammation frequently affect postmenopausal women or estrogen deprivation. Recent research has focused on alternative therapies that can enhance these women's quality of life. This study set out to investigate the effects of physical exercise (EX) and intermittent fasting (IF) on oxidants/antioxidants, inflammatory cytokines, neurotransmitters, and brain-derived neurotrophic factor (BDNF) in the cortex of rats. Additionally, it sought to assess the response to oxidative stress and neuroinflammation in the brains of rats following ovariectomy (OVX) and the potential mechanisms of these interventions. Fifty female rats were divided into one of the following groups 30 days after bilateral OVX: Control, OVX, OVX + EX, OVX + IF, and OVX + EX + IF groups. The rats in the Control and OVX groups continued their normal activities and had unrestricted access to food and water, but the rats in the OVX + EX and OVX + EX + IF groups had a 4-week treadmill training program, and the rats in the OXV + IF and OVX + EX + IF groups fasted for 13 h each day. The rats were killed, the cerebral cortex was taken, tissue homogenates were created, and various parameters were estimated using these homogenates. The results show that ovariectomized rats had decreased levels of neurotransmitters (DA, NE, and SE), acetylcholinesterase, brain GSH (glutathione), SOD (superoxide dismutase), catalase, GPx (glutathione peroxidase), and TAC (total antioxidant capacity), as well as elevated levels of proinflammatory cytokines and mediators (TNF-α, IL-1β, Cox-2). While ovariectomy-induced declines in neurotransmitters, enzymatic and nonenzymatic molecules, neuroinflammation, and oxidative brain damage were considerably mitigated and prevented by treadmill exercise and intermittent fasting, BDNF was significantly increased. These results suggest that ovariectomy can impair rat neuronal function and regular treadmill exercise and intermittent fasting seem to protect against ovariectomy-induced neuronal impairment through the inhibition of oxidative stress and neuroinflammation and increased BDNF levels in the brain cortex. However, combining regular exercise and intermittent fasting did not provide additional benefits compared to either treatment alone.

Effectiveness of high-intensity interval training on peripheral brain-derived neurotrophic factor in adults: Asystematic review and network meta-analysis.

High-intensity interval training (HIIT) has emerged as an alternative training method to increase brain-derived neurotrophic factor (BDNF) levels, a crucial molecule involved in plastic brain changes. Its effect compared to moderate-intensity continuous training (MICT) is controversial. We aimed to estimate, and to comparatively evaluate, the acute and chronic effects on peripheral BDNF levels after a HIIT, MICT intervention or a control condition in adults. The CINAHL, Cochrane, PubMed, PEDro, Scopus, SPORTDiscus, and Web of Science databases were searched for randomized controlled trials (RCTs) from inception to June 30, 2023. A network meta-analysis was performed to assess the acute and chronic effects of HIIT versus control condition, HIIT versus MICT and MICT versus control condition on BDNF levels. Pooled standardized mean differences (SMDs) and their 95% confidence intervals (95% CIs) were calculated for RCTs using a random-effects model. A total of 22 RCTs were selected for the systematic review, with 656 participants (aged 20.4-79 years, 34.0% females) and 20 were selected for the network meta-analysis. Network SMD estimates were significant for HIIT versus control condition (1.49, 95% CI: 0.61, 2.38) and MICT versus control condition (1.08, 95% CI: 0.04, 2.12) for acutely BDNF increase. However, pairwise comparisons only resulted in a significant effect for HIIT versus control condition. HIIT is the best training modality for acutely increasing peripheral BDNF levels in adults. HIIT may effectively increase BDNF levels in the long term.

Amisulpride attenuates 5-fluorouracil-induced cognitive deficits via modulating hippocampal Wnt/GSK-3β/β-catenin signaling in Wistar rats

Chemotherapy-induced cognitive impairment (CICI) is a general term describing cognitive dysfunction during/after treatment with chemotherapeutic agents. CICI represents a significant medical problem due to its increasing prevalence with the lack of robust therapeutic approaches. This study aimed at investigating the effects of chronic treatment with amisulpride (5 mg/kg/day) in the management of 5-fluorouracil (5-FU)-induced cognitive deficits in Wistar rats. Rats received 5 intraperitoneal injections of 5-FU (25 mg/kg every 3 days). 5-FU treatment induced impairments in spatial learning (reduction in object location discrimination ratio) and non-spatial learning (reduction in novel object recognition discrimination ratio). Moreover, 5-FU induced a decrease in the activity of the Wnt/GSK-3β/β-catenin pathway with a decrease in brain-derived neurotrophic factor (BDNF) level in the hippocampus. These changes were associated with an increase in the expression of the pro-inflammatory cytokines; tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in hippocampal tissue sections accompanied by a decrease in the number of Ki-67 positive cells (indicating a decrease in proliferative capacity), a decrease in the Nissl’s granules optical density (denoting neurodegeneration), a decrease in the number of viable intact neurons with an increase in the expression of β-amyloid and caspase-3. Amisulpride enhanced Wnt/GSK-3β/β-catenin signaling, increased BDNF levels, and abrogated 5-FU-induced neuroinflammation, apoptosis, β-amyloid accumulation, and neurodegenerative changes with an improvement of cognitive performance. This study draws attention to the pro-cognitive effects of amisulpride in 5-FU-exposed rats that could be attributed to enhancing hippocampal Wnt/GSK-3β/β-catenin signaling pathway, and this could offer a promising therapeutic option for subjects with CICI.

Beneficial effects of physical exercise and an orally active mGluR2/3 antagonist pro-drug on neurogenesis and behavior in an Alzheimer's amyloidosis model.

Modulation of physical activity represents an important intervention that may delay, slow, or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). One mechanism proposed to underlie the beneficial effect of physical exercise (PE) involves the apparent stimulation of adult hippocampal neurogenesis (AHN). BCI-838 is a pro-drug whose active metabolite BCI-632 is a negative allosteric modulator at group II metabotropic glutamate receptors (mGluR2/3). We previously demonstrated that administration of BCI-838 to a mouse model of brain accumulation of oligomeric AβE22Q (APP E693Q = "Dutch APP") reduced learning behavior impairment and anxiety, both of which are associated with the phenotype of Dutch APP mice. 3-month-old mice were administered BCI-838 and/or physical exercise for 1 month and then tested in novel object recognition, neurogenesis, and RNAseq. Here we show that (i) administration of BCI-838 and a combination of BCI-838 and PE enhanced AHN in a 4-month old mouse model of AD amyloid pathology (APP KM670/671NL /PSEN1 Δexon9= APP/PS1), (ii) administration of BCI-838 alone or with PE led to stimulation of AHN and improvement in recognition memory, (iii) the hippocampal dentate gyrus transcriptome of APP/PS1 mice following BCI-838 treatment showed up-regulation of brain-derived neurotrophic factor (BDNF), PIK3C2A of the PI3K-mTOR pathway, and metabotropic glutamate receptors, and down-regulation of EIF5A involved in modulation of mTOR activity by ketamine, and (iv) validation by qPCR of an association between increased BDNF levels and BCI-838 treatment. Our study points to BCI-838 as a safe and orally active compound capable of mimicking the beneficial effect of PE on AHN and recognition memory in a mouse model of AD amyloid pathology.

Exploring the Preliminary Effects of Resistance Training on Total Brain-Derived Neurotrophic Factor (BDNF) Levels in Elderly Individuals: A Pilot Study

Background: Studies have shown that exercise modulates brain-derived neurotrophic factor (BDNF) levels, and resistance training, in particular, has received increasing attention for its potential to enhance BDNF production. Most studies investigating exercise-induced BDNF changes have focused on free or mature BDNF, while the measurement of total BDNF, encompassing both proBDNF and mature BDNF, may provide a more comprehensive understanding of BDNF regulation. This pilot study aimed to explore the preliminary effects of resistance training on total BDNF levels in elderly individuals participating in a resistance training program.&#x0D; Methods: A small sample of participants (n=6) was recruited and engaged in a structured resistance training program for 12 weeks, with 6 participants in a control group. Total BDNF levels were measured at baseline and post-intervention using reliable laboratory assessments. Additionally, an isokinetic dynamometer was used to determine muscle strength to explore the effect of the resistance training program on muscle performance.&#x0D; Results: The findings revealed a significant increase in total BDNF levels following the 12 week resistance training intervention (p&lt;0.05). However, improvements in physical performance measures, knee extension peak torque and isometric maximal voluntary contraction, were not observed.&#x0D; Conclusion: In conclusion, this pilot study provides preliminary evidence of the positive effects of a 12 week resistance training intervention on total BDNF levels. The measurement of total BDNF levels serves as an important marker in assessing the response to resistance training. Further research with larger sample sizes and longer intervention periods is warranted to further explore the relationship between resistance training and total BDNF levels and to confirm these preliminary findings. Understanding the impact of resistance training on total BDNF levels can have implications for optimizing training programs and potentially improving exercise-related outcomes.&#x0D; Keywords: muscle strength, exercise, brain-derived neurotrophic factor, neuroplasticity, healthy ageing.

The Influence of Electroconvulsive Therapy (ECT) on Brain-Derived Neurotrophic Factor (BDNF) Plasma Level in Patients with Schizophrenia-A Systematic Review and Meta-Analysis.

The main aim of this systematic review and meta-analysis is to establish whether there is a correlation between the brain-derived neurotrophic factor (BDNF) level and electroconvulsive therapy (ECT) treatment and the reduction in psychotic symptoms in patients diagnosed with schizophrenia. A systematic search of PubMed/Medline, Cochrane Library, Web of Science, Scopus and Embase was conducted up to March 2023. Inclusion criteria: studies in which adult patients with schizophrenia treated with antipsychotic medication received ECT therapy and had the BDNF level measured before and after ECT treatment. Exclusion criteria: animal and in vitro studies or studies not involving complete information about the treatment and concentration of BDNF in plasma. The risk of bias was assessed using Egger's regression-based test for meta-analysis with continuous outcomes. Six studies comprising 248 individuals with schizophrenia were included. A statistically significant increase in BDNF levels after ECT treatment was observed only in two studies (p < 0.001 and p < 0.027, respectively), whereas in four other studies, an upward trend without statistical significance was noticed. The estimated overall size effect revealed that ECT therapy caused a slight change in the BDNF level but without statistical significance (ES = -0.328). Different numbers of ECT procedures (4-10), final measurement of the BDNF level made at a different time point, using bilateral or unilateral electrode positioning during ECT and treatment with different combinations of typical or atypical antipsychotic medications may be potential reasons for the lack of statistical significance in the changes in BDNF levels after treatment. Data regarding the measurement of BDNF levels pre and post ECT therapy in patients with schizophrenia are very limited without an extended follow-up period and evaluation of mental health change. Our meta-analysis showed that treatment with ECT therapy and antipsychotic medication increases serum BDNF levels in patients with drug-resistant schizophrenia compared to patients treated with medication only; however, this effect is not statistically significant.