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Serum and plasma brain-derived neurotrophic factor and response in a randomized controlled trial of riluzole for treatment resistant depression.
Wilkinson, ST, Kiselycznyk, C, Banasr, M, Webler, RD, Haile, C, Mathew, SJ
Journal of affective disorders. 2018;:514-518
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Abstract
BACKGROUND Serum brain-derived neurotrophic factor (BDNF) is decreased in individuals with major depressive disorder (MDD). Pre-clinical and clinical reports suggest that the glutamate release inhibitor riluzole increases BDNF and may have antidepressant properties. Here we report serum (sBDNF) and plasma (pBDNF) levels from a randomized controlled, adjunctive, sequential parallel comparison design trial of riluzole in MDD. METHODS Serum and plasma BDNF samples were drawn at baseline and weeks 6 and 8 from 55 subjects randomized to adjunctive treatment with riluzole or placebo for 8 weeks. RESULTS Riluzole responders had lower baseline serum (19.08 ng/ml [SD 9.22] v. 28.80 ng/ml [9.63], p = 0.08) and plasma (2.72 ng/ml [1.07] v. 4.60 ng/ml [1.69], p = 0.06) BDNF compared to non-responders at a trend level. This pattern was nominally seen in placebo responders for baseline pBDNF to some degree (1.21 ng/ml [SD 1.29] v. 3.58 ng/ml [SD 1.67], p = 0.12) but not in baseline sBDNF. LIMITATIONS A number of limitations warrant comment, including the small sample size of viable BDNF samples and the small number of riluzole responders. CONCLUSIONS Preliminary evidence reported here suggests that lower baseline BDNF may be associated with better clinical response to riluzole.
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RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet.
de Luis, DA, Fernández Ovalle, H, Izaola, O, Primo, D, Aller, R
Journal of diabetes and its complications. 2018;(2):216-220
Abstract
BACKGROUND Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients. OBJECTIVE Our aim was to analyze the effects of rs10767664 BDNF gene polymorphism on body weight, cardiovascular risk factors and serum adipokine levels after a standard hypocaloric diet in obese subjects. DESIGN A Caucasian population of 80 obese patients was analyzed before and after 3months on a standard hypocaloric diet. RESULTS Fifty patients (62.5%) had the genotype AA and 30 (37.5%) subjects had the next genotypes; AT (25 patients, 31.3%) or TT (5 study subjects, 6.3%) (second group). In non T allele carriers, the decreases in weight-3.4±2.9kg (T allele group -1.7±2.0kg:p=0.01), BMI -1.5±0.2kg (T allele group -1.2±0.5kg:p=0.02), fat mass-2.3±1.1kg (T allele group -1.7±0.9kg:p=0.009), waist circumference-3.8±2.4cm (T allele group -2.1±3.1cm:p=0.008), triglycerides -13.2±7.5mg/dl (T allele group +2.8±1.2mg/dl:p=0.02), insulin -2.1±1.9mUI/L (T allele group -0.3±1.0mUI/L:p=0.01), HOMA-IR -0.9±0.4 (T allele group -0.1±0.8:p=0.01) and leptin -10.1±9.5ng/dl (T allele group -3.1±0.2ng/dl:p=0.01) were higher than T allele carriers. CONCLUSION rs10767664 variant of BDNF gene modify anthropometric and biochemical changes after weight loss with a hypocaloric diet.
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Relevance of polymorphisms in MC4R and BDNF in short normal stature.
Herrfurth, N, Volckmar, AL, Peters, T, Kleinau, G, Müller, A, Cetindag, C, Schonnop, L, Föcker, M, Dempfle, A, Wudy, SA, et al
BMC pediatrics. 2018;(1):278
Abstract
BACKGROUND Variation in genes of the leptinergic-melanocortinergic system influence both body weight and height. Because short normal stature (SNS) is characterized by reduced body height, delayed maturation and leanness, allelic variation of genes in this pathway are hypothesized to affect this common condition. METHODS We analyzed the coding regions of LEP, MC4R, MRAP2 and BDNF in 185 children with SNS (height < 5th percentile) to search for non-synonymous and frameshift variants. For association studies (two-sided χ2-tests) population-based data sets (ExAC, EVS and KORA) were used. Cyclic AMP accumulation, cell surface expression, central expression and MAP kinase activation were assayed in vitro to determine the functional implications of identified variants. RESULTS We detected eleven variants predicted to be protein-altering, four in MC4R, four in BDNF, and three in MRAP2. No variants were found in LEP. In vitro analysis implied reduced function for the MC4R variant p.Met215Ile. Loss-of-function is contrary to expectations based on obesity studies, and thus does not support that this variant is relevant for SNS. The minor SNP alleles at MC4R p.Val103Ile and BDNF p.Val66Met were nominally associated with SNS. CONCLUSION Taken together, although genes of the leptinergic-melanocortinergic system are important for normal growth, our data do not support the involvement of rare mutations in LEP, MC4R, MRAP2 or BDNF in short normal stature.
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Differences in brain-derived neurotrophic factor between neonates born to mothers with normal and low ferritin.
Yusrawati, , Rina, G, Indrawati, LN, Machmud, R
Asia Pacific journal of clinical nutrition. 2018;(2):389-392
Abstract
BACKGROUND AND OBJECTIVES Maternal iron deficiency in late pregnancy, labor, and the postpartum period has an indirect impact to decrease neurotrophin concentration in the fetal hippocampus, namely brain-derived neurotrophic factor (BDNF). It plays an important role in the development of learning, memory, and behavior. The aim of this study was to determine the differences in BDNF between neonates born to mothers with normal and low ferritin. METHODS AND STUDY DESIGN This was an observational study with a cross-sectional design involving 20 term pregnant women with normal ferritin (>=12 ng/mL) and 20 term pregnant women with low ferritin (<12 ng/mL). Samples were taken from Yarsi hospital, BMC hospital, and Hardi clinic located in Padang, from August 2015 to February 2016. Umbilical cord plasma was examined directly after delivery using an enzymelinked immunosorbent assay (ELISA) employed at the Biomedical Laboratory of Andalas University. Mean differences were statistically assessed by independent samples t-test. RESULTS Plasma BDNF concentrations in neonates born to mothers with normal and low ferritin were 3.81±1.37 ng/mL and 2.78±1.19 ng/mL, respectively (p=0.015). CONCLUSIONS Plasma BDNF was lower in neonates born to mothers with low serum ferritin.
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Impact of prolonged neuromuscular electrical stimulation on metabolic profile and cognition-related blood parameters in type 2 diabetes: A randomized controlled cross-over trial.
Miyamoto, T, Iwakura, T, Matsuoka, N, Iwamoto, M, Takenaka, M, Akamatsu, Y, Moritani, T
Diabetes research and clinical practice. 2018;:37-45
Abstract
AIMS: This study aimed to examine the effect of prolonged neuromuscular electrical stimulation (NMES) on the metabolic profile and cognition-related blood parameters in patients with type 2 diabetes mellitus (T2DM). METHODS Fourteen patients with T2DM (63.2 ± 3.0 years, 76.1 ± 3.5 kg) participated in a randomized controlled cross-over study, in which 8-week-long NMES interventions were performed on both legs. The NMES training protocol consisted of 40-min sessions, 5 days per week, for 8 weeks. The relative changes in glucose and lipid profiles, and cognition-related blood parameters were evaluated. RESULTS NMES training induced significant changes in the fasting glucose concentration (p < 0.05) and percent body fat (p < 0.05), although there were no significant changes in HbA1c and blood lipid levels (p ≥ 0.05). The change in plasma brain-derived neurotrophic factor (BDNF) levels was significantly higher in the NMES period than in the control period (p < 0.05). CONCLUSIONS This study showed that an 8-week NMES training program could induce greater changes in the blood glucose concentration, percent body fat, and plasma BDNF levels than the control intervention in patients with T2DM. NMES training might prove to be an alternative exercise method for patients who might have difficulties in performing adequate voluntary exercise.
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Peripheral Blood Brain-Derived Neurotrophic Factor as a Biomarker of Alzheimer's Disease: Are There Methodological Biases?
Balietti, M, Giuli, C, Conti, F
Molecular neurobiology. 2018;(8):6661-6672
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Abstract
Mounting evidence that alterations in brain-derived neurotrophic factor (BDNF) levels and signaling may be involved in the etiopathogenesis of Alzheimer's disease (AD) has suggested that its blood levels could be used as a biomarker of the disease. However, higher, lower, or unchanged circulating BDNF levels have all been described in AD patients compared to healthy controls. Although the reasons for such different findings are unclear, methodological issues are likely to be involved. The heterogeneity of participant recruitment criteria and the lack of control of variables that influence circulating BDNF levels regardless of dementia (depressive symptoms, medications, lifestyle, lack of overlap between serum and plasma, and experimental aspects) are likely to bias result and prevent study comparability. The present work reviews a broad panel of factors, whose close control could help reduce the inconsistency of study findings, and offers practical advice on their management. Research directed at elucidating the weight of each of these variables and at standardizing analytical methodologies is urgently needed.
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Association of Brain-derived neurotrophic factor gene polymorphisms with body mass index: A systematic review and meta-analysis.
Akbarian, SA, Salehi-Abargouei, A, Pourmasoumi, M, Kelishadi, R, Nikpour, P, Heidari-Beni, M
Advances in medical sciences. 2018;(1):43-56
Abstract
BACKGROUND Many studies with inconsistent results have assessed the association of Brain-derived neurotrophic factor (BDNF) gene polymorphisms with prevalence of obesity and overweight. This review aims to provide a summary of the literature evaluating the relation between BDNF genotype and body mass index (BMI). METHODS A systematic search through PubMed, Scopus, Science direct, Ovid and Cochrane was performed. We included observational studies with cross-sectional and case-control design, which investigated relationship between all kinds of BDNF polymorphisms with BMI, as a representative index of obesity and overweight. Newcastle-Ottawa Scale was used to assess the quality of included articles. RESULTS Thirty five studies were included in quantitative synthesis. Analyses were performed separately using OR, β coefficient and mean. Significant association were documented between rs925946 and BMI (OR=1.12, 95% CI=1.08-1.17, P heterogeneity=0.317), rs10501087 and BMI (OR=1.14, 95% CI=1.04-1.24, P heterogeneity=0.861), rs6265 and BMI (OR=1.13, 95% CI=1.07-1.19, P heterogeneity=0.406), rs988712 and BMI (OR=1.29, 95% CI=1.18-1.40, P heterogeneity=0.602). According to pooled β coefficient analysis, significant result was only observed in the rs925946 polymorphism subgroup. Pooled mean analysis showed that overall effects for the association between BDNF polymorphisms and BMI were not statistically significant. CONCLUSION This meta-analysis suggests that some polymorphisms in BDNF gene including rs925946, rs10501087, rs6265 and rs988712 can be considered as genetic determinants of obesity.
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Head-out immersion in hot water increases serum BDNF in healthy males.
Kojima, D, Nakamura, T, Banno, M, Umemoto, Y, Kinoshita, T, Ishida, Y, Tajima, F
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2018;(6):834-839
Abstract
PURPOSE Brain-derived neurotrophic factor (BDNF) is an important neurotrophin. The present study investigated the effects of head-out water immersion (HOI) on serum BDNF concentrations. METHODS Eight healthy men performed 20 min head-out water immersion at 42 °C (hot-HOI) and 35 °C (neutral-HOI). These experimental trials were administered in a randomised order separated by at least 7 days. Venous blood samples were withdrawn at rest, immediately after the 20-min HOI, as well as at 15 and 30 min after the end of the HOI. Serum BDNF and S100β, plasma cortisol, platelet and monocyte counts, and core body temperature (Tcb) were measured. RESULTS Tcb was higher at the end of the hot-HOI and 15 min after hot-HOI (p < 0.01), but recovered to pre-HOI level at 30 min after hot-HOI. No change in Tcb was recorded during neutral-HOI. BDNF level was higher (p < 0.05) at the end of the hot-HOI and at 15 min after the end of hot-HOI, and returned to the baseline at 30 min after hot-HOI. S100β, platelet count and monocyte count remained stable throughout the study. Cortisol level was lower at the end of the hot-HOI and returned to pre-HOI level during the recovery period. BDNF and S100β, cortisol, and platelet and monocyte counts did not change throughout the neutral-HOI study. CONCLUSIONS The present findings suggested that the increase in BDNF during 20-min hot-HOI was induced by hyperthermia through enhanced production, rather than by changes in permeability of the blood-brain barrier (BBB), platelet clotting mechanisms or secretion from monocytes.
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The effects of curcumin on brain-derived neurotrophic factor and cognition in schizophrenia: A randomized controlled study.
Wynn, JK, Green, MF, Hellemann, G, Karunaratne, K, Davis, MC, Marder, SR
Schizophrenia research. 2018;:572-573
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Developmental origins of adult health and disease: The metabolic role of BDNF from early life to adulthood.
Briana, DD, Malamitsi-Puchner, A
Metabolism: clinical and experimental. 2018;:45-51
Abstract
Accumulating evidence suggests that the origins of adult disease may occur during fetal life. Thus, the concept of "developmental programming" has been introduced and supported by epidemiological and experimental data. This concept supports the idea that the nutritional and hormonal status during pregnancy could interfere in metabolism control. The mechanisms responsible for this "developmental programming" remain poorly documented. Current research indicates that neurotrophins and particularly brain-derived neurotrophic factor (BDNF) may play a crucial role in this process. Although mainly expressed in the nervous system, BDNF and its receptor, tropomyosin-related kinase B (TrkB), are immunolocalized in several regions of the human placenta and have important functions during pregnancy. BDNF serves widespread roles in regulating energy homeostasis in both fetuses and adults, by controlling patterns of fetal growth, adult feeding and physical activity, and by regulating glucose metabolism in peripheral tissues. Impaired BDNF signaling may be implicated in the etiopathogenesis of the metabolic syndrome. Novel BDNF-focused interventions are being developed for obesity, diabetes and neurological disorders. The aim of this article is to provide a brief comprehensive literary review regarding the potential implications of BDNF in "developmental programming", through regulation of metabolism and energy balance from early life to adulthood.