Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging.Read more
Brain-derived neurotrophic factor (BDNF) plays a critical role in sensorimotor recovery after a stroke. However, few studies have assessed the circulating BDNF levels in post-stroke humans to understand its changes. This study was conducted to measure BDNF serum concentrations in subjects with chronic hemiparesis, as well as to correlate serum concentrations with age, post-stroke time, total score of Stroke Specific Quality of Life Scale (SS-QOL), mobility subscale score, and motor function of SS-QOL.
Seventeen chronic post-stroke subjects matched by age and gender with healthy controls took part in the study. Personal data (age, hemiparesis side, and post-stroke time) were collected, and a physical examination (weight, height, body mass index) and SS-QOL assessment were carried out. On the same day, after the initial evaluation, venous blood samples were collected from the chronic post-stroke subjects and the healthy subjects. The BDNF serum concentrations were measured blindly by enzyme-linked immunosorbent assay.
Subjects with chronic hemiparesis presented a decrease in BDNF serum compared with healthy subjects (P < .01). There was no correlation between BDNF serum levels with post-stroke time, age or quality of life, mobility, and the upper extremity motor function (P > .05). BDNF concentrations are related to structural and functional recovery after stroke; thus, this reduction is important to understand the rehabilitation process more clearly. However, more studies are needed considering the genetic variations and other tools to assess motor impairment and functional independence.
Chronic post-stroke subjects presented a decrease in BDNF serum concentrations, without a correlation with post-stroke time, age, and quality of life.Read more
It was shown for the first time that the endogenous cyclic dipeptide cycloprolylglycine (CPG) at concentrations of 10(-7) and 10(-3) M and piracetam at a concentration of 10(-3) M increased the content of brainderived neurotrophic factor (BDNF) in the culture of neuronal cells in normal state and under conditions of glutamate and 6-oxydopamine neurotoxicity. This may indicate the possible involvement of BDNF in the mechanism of action of neuropeptide CPG and piracetam.Read more
Zinc plays an important role in regulating the expression of brain-derived neurotrophic factor (BDNF) and its receptor in nervous system, but the correlation among Zn(2+), zinc transporter, and BDNF in spinal cord injuries (SCI) is not fully understood. The purpose of this study was to investigate the expression of Zn(2+), zinc transporter 1 (ZnT-1), and BDNF, as well as their correlation in spinal cord-injured rats. One hundred Wistar male rats were divided into two groups: sham-operated group (as control group) and model group. Spinal cord injury was induced in model groups by hemisection of T9 on the left side. Compared with the control group, the serum zinc levels in SCI model group were significantly decreased after surgery, but zinc concentrations in spinal cord were increased gradually. The mRNA levels of ZnT-1 and BDNF were significantly increased in SCI model group, and there is a positive correlation between them (Spearman rho = 0.381, P = 0.0204). The correlation found between BDNF and ZnT-1 allows us to speculate that these two factors may be physiologically co-regulated, which may provide an idea for the treatment of SCI.Read more
Streptococcus agalactiae (GBS) is a major cause of severe morbidity and mortality in neonates and young infants, causing sepsis, pneumonia and meningitis. The survivors from this meningitis can suffer serious long-term neurological consequences, such as, seizures, hearing loss, learning and memory impairments. Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) control the neuronal cell death during the brain development and play an important role in neuronal differentiation, survival and growth of neurons. Neonate Wistar rats, received either 10μL of sterile saline as a placebo or an equivalent volume of GBS suspension at a concentration of 1×10(6)cfu/mL. Sixty days after induction of meningitis, the animals underwent behavioral tests, after were killed and the hippocampus and cortex were retired for analyze of the BDNF and NGF levels. In the open-field demonstrated no difference in motor, exploratory activity and habituation memory between the groups. The step-down inhibitory avoidance, when we evaluated the long-term memory at 24h after training session, we found that the meningitis group had a decrease in aversive memory when compared with the long-term memory test of the sham group. BDNF levels decreased in hippocampus and cortex; however the NGF levels decreased only in hippocampus. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to GBS meningitis.Read more
Neuritin 1 gene (NRN1) is involved in neurodevelopment processes and synaptic plasticity and its expression is regulated by brain-derived neurotrophic factor (BDNF). We aimed to investigate the association of NRN1 with schizophrenia-spectrum disorders (SSD) and bipolar disorders (BPD), to explore its role in age at onset and cognitive functioning, and to test the epistasis between NRN1 and BDNF.
The study was developed in a sample of 954 SSD/BPD patients and 668 healthy subjects. Genotyping analyses included 11 SNPs in NRN1 and one functional SNP in BDNF.
The frequency of the haplotype C-C (rs645649-rs582262) was significantly increased in patients compared to controls (P = 0.0043), while the haplotype T-C-C-T-C-A (rs3763180-rs10484320-rs4960155-rs9379002-rs9405890-rs1475157) was more frequent in controls (P = 3.1 × 10(-5)). The variability at NRN1 was nominally related to changes in age at onset and to differences in intelligence quotient, in SSD patients. Epistasis between NRN1 and BDNF was significantly associated with the risk for SSD/BPD (P = 0.005).
Results suggest that: (i) NRN1 variability is a shared risk factor for both SSD and BPD, (ii) NRN1 may have a selective impact on age at onset and intelligence in SSD, and (iii) the role of NRN1 seems to be not independent of BDNF.Read more
Brain-derived neurotrophic factor (BDNF) is associated with the risk for Alzheimer's disease and type 2 diabetes. The aim of this study was to examine the association of BDNF variants with type 2 diabetes and the interactions of different BDNF genotypes with dietary habits and food and nutrient intakes in middle-aged adults.
The study population included 8840 adults ages 40 to 65 y from the Ansan and Asung areas in the Korean Genome Epidemiology Study, a cross-sectional study of Korean adults, conducted from 2001 to 2002. Adjusted odd ratios for the prevalence of glucose intolerance and type 2 diabetes according to BDNF genotypes were calculated after adjusting for age, sex, residence area, body mass index, physical activity, and smoking and stress status. Nutrient intake was calculated from usual food intake determined by semiquantitative food frequencies using the nutrient assessment software.
BDNF rs6265 Val/Met and Met/Met variants were negatively associated with the risk for type 2 diabetes after adjusting for covariates. Serum glucose levels after glucose loading and hemoglobin A1c, but not serum insulin levels, also were negatively associated with BDNF Val/Met and Met/Met. In subgroup analysis, sex and stress levels had an interaction with BDNF Val/Met in the risk for type 2 diabetes. Glucose-intolerant and diabetic, but not nondiabetic, patients with BDNF Met/Met had nominally, but significantly higher intakes of energy than those with BDNF Val/Val. BDNF rs6265 had consistent gene-diet interactions with energy and protein intake. With low-energy, low-protein, and high-carbohydrate intake, BDNF Val/Met lowered the risk for type 2 diabetes after adjusting for confounding factors. BDNF Val/Met did not compensate for developing type 2 diabetes with high-energy intake. Additionally, indexes of insulin resistance and insulin secretion showed the same gene-energy interaction as type 2 diabetes.
BDNF Val/Met and Met/Met variants (rs6265) decreases the risk for glucose intolerance and type 2 diabetes. BDNF variants interacted with nutrient intake, especially energy and protein intake: Middle-aged individuals with BDNF Val/Val are prone to developing type 2 diabetes even with low energy and protein intake.Read more
In order to analyze the association of CNR1(Cannabinoid receptor 1), GAD1(Glutamate decarboxylase 1), and BDNF(Brain-derived neurotrophic factor) polymorphisms with male heroin dependence in the Dai population in Yunnan Province, an eight-SNP co-amplification protocol was established to genotype on the SNaPshot platform. A case-control study was performed with 8 SNPs from CNR1, GAD1, and BDNF genes in 165 heroin-dependent males and 170 healthy males of the Dai population. Statistical analyses were conducted with SPSS17.0, Haploview4.2, PHASE2.1, and MDR software. We found that: (1) the genotype frequency of rs13306221 was significant in the case group (P<0.025); (2) the A allelic frequency of rs6265 was significantly higher in the case group; (3) the haplotypes of T-A-C, C-C-C, C-C-T, and T-C-C based on rs1978340-rs3791878-rs11542313 and haplotype A-G based on rs6265-rs13306221 were significant (P<0.05); (4) the haplotype frequencies of T-A-C, C-C-T, and A-G were significantly higher in the case group. These results indicate that the linkage between rs1978340 and rs3791878 in GAD1 has a strong association with heroin dependence. Furthermore, polymorphisms in CNR1 (rs1049353), GAD1 (rs1978340 and rs11542313), and BDNF (rs6265 and rs13306221) were associated with heroin dependence in the Yunnan Dai population, and individuals with the rs6265 A allele were more likely to be heroin dependent.Read more
Major depression is a complex disorder characterized by genetic and environmental interactions. Selective serotonin reuptake inhibitors (SSRIs) effectively treat depression. Neurogenesis following chronic antidepressant treatment activates brain derived neurotrophic factor (BDNF) signaling. In this study, we analyzed the effects of the SSRI fluvoxamine (Flu) on locomotor activity and forced-swim behavior using chronic dexamethasone (cDEX) infusions in mice, which engenders depression-like behavior. Infusion of cDEX decreased body weight and produced a trend towards lower locomotor activity during darkness. In the forced-swim test, cDEX-mice exhibited increased immobility times compared with mice administered saline. Flu treatment reversed decreased locomotor activity and mitigated forced-swim test immobility. Real-time polymerase chain reactions using brain RNA samples yielded significantly lower BDNF mRNA levels in cDEX-mice compared with the saline group. Endoplasmic reticulum stress-associated X-box binding protein-1 (XBP1) gene expression was lower in cDEX-mice compared with the saline group. However, marked expression of the XBP1 gene was observed in cDEX-mice treated with Flu compared with mice given saline and untreated cDEX-mice. Expression of 5-HT2A and Sigma-1 receptors decreased after cDEX infusion compared with the saline group, and these decreases normalized to control levels upon Flu treatment. Our results indicate that the Flu moderates reductions in voluntary activity following chronic dexamethasone infusions in mice via recovery of BDNF signal cascades.Read more
Based on morphological and physiological characteristics, the mammalian neocortex is divided into various neocortical areas and its diversity is prominent in the primates including humans. These neocortical areas are constructed during development, but the details of the developmental events remain unclear, especially at the molecular level. We measured the mRNA and protein levels of neurotrophins in various neocortical areas of developing rhesus monkeys. The expression patterns of both the neurotrophin-3 (NT-3) mRNA and the protein showed area differences. In the sensory and motor areas, NT-3 mRNA and protein levels had started to decline by a week after birth. In contrast, the levels declined after the third postnatal week in the association neocortical areas. The level of brain-derived neurotrophic factor (BDNF) protein changed in an area-dependent manner during development, but that of mRNA did not. The decline of the BDNF protein level started earlier in the sensory and motor neocortical areas than in the association neocortical areas, suggesting that sensory and motor neocortical areas develop earlier than the association areas in terms of the developmental changes in neurotrophins.Read more