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1.
Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity and Metformin Treatment in Adult Patients With Type 2 Diabetes Mellitus.
Eyileten, C, Mirowska-Guzel, D, Milanowski, L, Zaremba, M, Rosiak, M, Cudna, A, Kaplon-Cieslicka, A, Opolski, G, Filipiak, KJ, Malek, L, et al
Canadian journal of diabetes. 2019;(1):19-26
Abstract
OBJECTIVES The aim of this study was to investigate the association of serum brain-derived neurotrophic factor (BDNF) levels with platelet reactivity and antidiabetes treatment, as well as serum adipocytokine concentrations. METHODS This observational, open-label study enrolled 149 patients. Serum BDNF, hematologic, biochemical parameters and platelet reactivity were measured. Blood samples were taken after the last acetylsalicylic acid dose. RESULTS Patients with high BDNF levels were younger (65.60±8.956 vs. 68.59±8.516) and smoked cigarettes more frequently (14.6% vs. 4.1%); they were more commonly being treated by metformin (77.3% vs. 54%); had higher platelet counts (245.81±68.85 103/mm3 vs. 206.61±44.48 103/mm3); had shorter collagen-adenosine diphosphate closure time (CADP-CT) values (104.88±69.73 s vs. 140.93±86.63 s); had higher triglyceride concentrations (140.73±67.5 vs. 121.76±60.49) and had higher concentrations of serum thromboxane B2 (0.938±1.59 vs. 0.364±0.76). In univariate linear regression analyses, predictive factors for serum BDNF levels above the median were metformin treatment, current smoking, platelet count, triglyceride concentration, total cholesterol concentration and CADP-CT >74 s. In multivariate backward stepwise analysis CADP-CT >141 s; adiponectin concentration >4.22 µg/mL; total cholesterol and low-density lipoprotein levels were independently associated with serum BDNF levels above the median. CONCLUSIONS Our results suggest that BDNF may be associated with lipid metabolism and that increased production of BDNF may be related to metformin treatment. Moreover, we showed an association between BDNF levels and platelet reactivity; we found that serum BDNF levels in patients with type 2 diabetes who had high platelet reactivity were higher than in subjects with normal platelet reactivity despite antiplatelet therapy.
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2.
Sedentarism, Physical Activity, Steps, and Neurotrophic Factors in Obese Children.
Mora-Gonzalez, J, Migueles, JH, Esteban-Cornejo, I, Cadenas-Sanchez, C, Pastor-Villaescusa, B, Molina-García, P, Rodriguez-Ayllon, M, Rico, MC, Gil, A, Aguilera, CM, et al
Medicine and science in sports and exercise. 2019;(11):2325-2333
Abstract
PURPOSE This study aimed to examine the associations of sedentary time, physical activity (PA) and step-related behaviors with neurotrophic growth factors. METHODS A total of 97 children with overweight/obesity age 8 to 11 yr participated in this study. Sedentary time, PA, and steps were measured by GT3X+ accelerometers in hip and nondominant wrist. Estimates of light, moderate, vigorous, and moderate-to-vigorous PA (MVPA) were obtained. Steps per daytime, peak 60-, 30-, and 1-min cadence were computed. The time accumulated (min·d) in different cadence bands of steps was also computed from hip accelerometer. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin growth factor-1 (IGF-1) were determined by the XMap technology (Luminex IS 100/200 system, Luminex Corporation, Austin, TX). RESULTS Light PA, moderate PA, MVPA, and the peak 60-min cadence were positively related with BDNF concentrations (all P < 0.05), and only light PA to VEGF (P = 0.048). No association was observed for IGF-1 (P > 0.05). The associations of light PA with BDNF and VEGF disappeared (all P > 0.05) after performing analyses with nondominant wrist-placement data. However, moderate PA and MVPA remained significantly associated with BDNF (both P < 0.05). The time accumulated in cadence bands of 40 to 59 steps per day and 60 to 79 steps per day (i.e., walking at slow pace) was positively associated with plasma BDNF (all P < 0.05). CONCLUSIONS In conclusion, PA is positively related to plasma BDNF, whereas no relationship was observed for VEGF or IGF-1. Higher amounts of time spent in slow walking cadence bands could increment BDNF levels. Exercise-based randomized controlled trials in children with overweight/obesity should be carried out to better understand the influence of PA behaviors on the neurotrophic factors.
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3.
Effects of medium-term green tea extract supplementation combined with CrossFit workout on blood antioxidant status and serum brain-derived neurotrophic factor in young men: a pilot study.
Sadowska-Krępa, E, Domaszewski, P, Pokora, I, Żebrowska, A, Gdańska, A, Podgórski, T
Journal of the International Society of Sports Nutrition. 2019;(1):13
Abstract
BACKGROUND Potential health benefits are attributed to the antioxidant properties of green tea polyphenolic compounds. The main aim of the study was to evaluate the effects of a six-week green tea extract (GTE) supplementation combined with CrossFit workout on blood antioxidant status and serum brain-derived neurotrophic factor (BDNF) in men. METHODS Sixteen young males involved in CrossFit training were randomized into two groups supplemented with GTE or placebo for six weeks. Each participant performed an exercise test for the evaluation of maximum oxygen uptake (VO2max) twice, i.e., before starting (1st trial) and after completing the supplementation combined with CrosFit workout (2nd trial). Venous blood samples were drawn at rest, immediately post-test and after one hour of recovery in order to estimate activities of antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], reduced glutathione [GR]), non-enzymatic antioxidants (reduced glutathione [GSH], uric acid [UA], total phenolics), total antioxidant capacity (FRAP), lipid peroxidation products (TBARS), and BDNF. RESULTS Except for a significantly higher SOD activity and FRAP level recorded at rest and post-exercise in the 2nd trial compared to the corresponding values in the 1st trial, no significant differences were recorded among other assayed measures such as CAT, GPx, GR, GSH and BDNF. Moreover, a percentage increase in FRAP level was twice as high after six weeks' GTE consumption than after placebo. Regardless of the trial, an increase in plasma UA concentration and a decrease in plasma total phenolics level were observed after exercise test. Plasma TBARS concentrations were significantly higher in PLA group after six weeks' CrossFit training, while in GTE group they were slightly lower compared to the corresponding values in the 1st trial. Moreover, there was a significant inverse correlation between FRAP and TBARS in the GTE-supplemented group (r = - 0.40, p < 0.05). CONCLUSIONS A six weeks' consumption of GTE had marginal effect on aerobic capacity and serum BDNF level in CrossFit-trained men, but it caused a marked increase in the blood antioxidant capacity and a moderate attenuation of the training-induced lipid peroxidation.
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4.
A Pilot Study of the Use of Dexmedetomidine for the Control of Delirium by Reducing the Serum Concentrations of Brain-Derived Neurotrophic Factor, Neuron-Specific Enolase, and S100B in Polytrauma Patients.
Li, Y, Yu, ZX, Ji, MS, Yan, J, Cai, Y, Liu, J, Yang, HF, Jin, ZC
Journal of intensive care medicine. 2019;(8):674-681
Abstract
BACKGROUND Delirium is very common among patients with polytrauma, although no suitable means exist to feasibly reduce the incidence and duration of delirium in these patients. Recent reports have suggested that continuous intravenous (IV) infusions of dexmedetomidine, rather than benzodiazepine, be administered for sedation to reduce the duration of delirium in this population. However, serum neuron-specific enolase (NSE), S100 calcium binding protein B (S100B), and brain-derived neurotrophic factor (BDNF) levels have not yet been investigated in polytrauma patients who received sedation with dexmedetomidine rather than other conventional sedatives. The aim of this study was to assess the association of blood BDNF, NSE, and S100B with the occurrence of delirium among polytrauma patients who had been sedated with dexmedetomidine. MATERIALS AND METHODS Consecutive patients were randomly assigned to 1 of 2 treatment study groups, namely the "dexmedetomidine group" or the "common group." This case-control study included 18 patients with delirium and 34 matched controls in a 63-bed general intensive care unit (ICU). Blood samples were collected from all patients upon ICU admission, on the day when delirium was diagnosed, and on days 3 and 5 following diagnosis. The serum levels of S100B, BDNF, and NSE were determined by enzyme-linked immunosorbent assay. The sedation levels and delirium were assessed using the Richmond Agitation and Sedation Scale and the Confusion Assessment Method for the ICU. RESULTS The median BDNF, NSE, and S100B concentrations were significantly lower in the dexmedetomidine group than in the common group on the day when delirium was diagnosed and on the third day after delirium was diagnosed. The rate of delirium was significantly lower in the dexmedetomidine group than in the common group. There were clear differences in the BDNF, NSE, and S100B levels between the 2 groups on the fifth day after delirium was diagnosed. CONCLUSIONS Our randomized controlled study suggests that the sedation of polytrauma patients with dexmedetomidine could help reduce the serum BDNF, S100B, and NSE levels, which appear to be associated with the occurrence of delirium in the dexmedetomidine group.
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5.
Changes in Circulating BDNF in relation to Sex, Diet, and Exercise: A 12-Week Randomized Controlled Study in Overweight and Obese Participants.
Glud, M, Christiansen, T, Larsen, LH, Richelsen, B, Bruun, JM
Journal of obesity. 2019;:4537274
Abstract
Circulating BDNF is higher in women than in men and suggested to be affected by changes in food intake, body weight, and exercise. The purpose of this study was to compare BDNF concentrations in women and men during a 12-week weight loss intervention. Using a previously published 12-week randomized study, serum BDNF was assessed at baseline and after 12 weeks using an enzyme-linked immunosorbent assay method. Fifty overweight or obese but healthy individuals (26 women, mean age of 36.4 ± 7.9 years; 24 men, mean age of 38.0 ± 5.9 years) were included and allocated into three groups: exercise-only (EXO; 12 weeks of aerobic exercise and isocaloric diet), diet-only (DIO; 8 weeks of very low energy diet (VLED 600 kcal/day) followed by a 4-week weight maintenance diet), or diet and exercise (DEX; 12 weeks of aerobic exercise in parallel with 8 weeks of VLED (800 kcal/day) followed by a 4-week weight maintenance diet). At baseline, BDNF levels were 25% higher in women compared to men (p=0.006). Body weight was reduced in all intervention groups (p < 0.006). Exercise (EXO group) induced a 22% reduction in circulating BDNF in men (p=0.037) and women (p=0.080). In the DIO and DEX groups, a significant reduction in BDNF levels (29.9%; p=0.035 and 32.5%; p=0.003, respectively) was observed in women but not in men. In conclusion, circulating BDNF was significantly changed by diet alone or combined with exercise in women and only by exercise alone in men. This suggests that changes in circulating BDNF depend on weight loss methods (diet/exercise) as well as sex.
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6.
Zinc supplementation does not influence serum levels of VEGF, BDNF, and NGF in diabetic retinopathy patients: a randomized controlled clinical trial.
Kheirouri, S, Naghizadeh, S, Alizadeh, M
Nutritional neuroscience. 2019;(10):718-724
Abstract
Objectives: This study was aimed to evaluate the effects of zinc (Zn) supplementation on serum levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in patients with diabetic retinopathy (DR). Methods: In this randomized clinical trial, 50 patients with DR were allocated into the Zn (n = 25) and placebo (n = 25) groups to receive 30 mg Zn gluconate or maltose dextrin per day, respectively, for three months. Metabolic parameters and blood pressure were measured. Serum levels of Zn were assessed by atomic absorption spectrophotometry and serum levels of VEGF, BDNF and NGF by ELISA. Results: Forty-five patients completed the intervention. Levels of VEGF, BDNF and NGF were not affected by the Zn supplementation. Levels of VEGF correlated negatively with levels of Zn and positively with BDNF and NGF. There was also a positive correlation between BDNF and NGF. Serum levels of VEGF, BDNF and NGF were negatively correlated with serum levels of the diabetic parameters measured. Conclusions: Strong positive relationship between the growth factors and their inverse association with metabolic factors is possibly suggesting the contribution of these factors in the pathogenesis of DR through acting in a same biological pathway.
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7.
Effects of macular xanthophyll supplementation on brain-derived neurotrophic factor, pro-inflammatory cytokines, and cognitive performance.
Stringham, NT, Holmes, PV, Stringham, JM
Physiology & behavior. 2019;:112650
Abstract
PURPOSE Oxidative and inflammatory processes play a major role in stress-induced neural atrophy. There is a wide body of literature linking oxidative and inflammatory stress with reductions in neurotrophic factors, stress resilience, and cognitive function. Based on their antioxidant and anti-inflammatory capacity, we investigated the effect of the dietary carotenoids lutein and zeaxanthin, along with the zeaxanthin isomer meso-zeaxanthin (collectively the "macular xanthophylls" [MXans]) on systemic brain-derived neurotrophic factor (BDNF) and anti-oxidant capacity (AOC), and the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. To investigate higher-order effects, we assessed cognitive performance. METHODS 59 young (18-25 yrs.), healthy subjects participated in a 6-month, double-blind, placebo-controlled trial to evaluate the effects of MXan supplementation on the aforementioned serum parameters and cognitive performance. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg/day total MXans; all measures were taken at baseline and 6 months. Blood was obtained via fasting blood draw, and MXan concentration in the retina (termed macular pigment optical density [MPOD]) was measured via customized heterochromatic flicker photometry. Serum BDNF and cytokines were assessed via ELISA. Serum antioxidant capacity (AOC) and serum MXan concentrations were quantified via colorimetric microplate assay, and high-performance liquid chromatography, respectively. Cognitive performance was measured via a computer-based assessment tool (CNS Vital Signs). RESULTS BDNF, MPOD, serum MXans, and AOC all increased significantly versus placebo in both treatment groups over the 6-month study period (p < .05 for all). IL-1β decreased significantly versus placebo in both treatment groups (p = .0036 and p = .006, respectively). For cognitive measures, scores for composite memory, verbal memory, sustained attention, psychomotor speed, and processing speed all improved significantly in treatment groups (p < .05 for all) and remained unchanged in the placebo group. Several measures were found to be significantly associated in terms of relational changes over the course of the study. Notably, change in BDNF was related to change in IL-1β (r = -0.47; p < .001) and MPOD (r = 0.44; p = .0086). Additionally, changes in serum MXans were strongly related to AOC (r = 0.79 & 0.61 for lutein and zeaxanthin isomers respectively; p < .001). For cognitive scores, change in BDNF was correlated to change in composite memory (r = 0.32; p = .014) and verbal memory (r = 0.35; p = .007), whereas change in MPOD was correlated with change in both psychomotor speed (r = 0.38; p = .003), and processing speed (r = 0.35; p = .007). Change in serum lutein was found to be significantly correlated to change in verbal memory (r = 0.41; p < .001), composite memory (r = 0.31; p = .009), and sustained attention (r = 0.28; p = .036). Change in serum zeaxanthin isomers was significantly correlated with change in verbal memory (r = 0.33; p = .017). Lastly, change in AOC was significantly associated with verbal memory (r = 0.34; p = .021), composite memory (r = 0.29; p = .03), and sustained attention (r = 0.35; p = .016). No significant relational changes in any cognitive parameter were found for the placebo group. CONCLUSIONS Six months of daily supplementation with at least 13 mg of MXans significantly reduces serum IL-1β, significantly increases serum MXans, BDNF, MPOD, and AOC, and improves several parameters of cognitive performance. Findings suggest that increased systemic antioxidant/anti-inflammatory capacity (and not necessarily deposition of the carotenoids in neural tissues), may explain many of the effects determined in this study. The significant relationship between change in BDNF and IL-1β over the course of the study suggests that regular consumption of MXans interrupts the inflammatory cascade that can lead to reduction of BDNF. Changes in MPOD and BDNF appear to account for enhancement in cognitive parameters that involve speed of processing and complex processing, respectively. ISRCTN Clinical Trial Registration: ISRCTN16156382.
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A cross-sectional study of fatty acids and brain-derived neurotrophic factor (BDNF) in human milk from lactating women following vegan, vegetarian, and omnivore diets.
Perrin, MT, Pawlak, R, Dean, LL, Christis, A, Friend, L
European journal of nutrition. 2019;(6):2401-2410
Abstract
PURPOSE Essential fatty acids are critical for brain growth and neurodevelopment in infancy. Maternal diet and supplement use have a significant impact on the fat composition of human milk. The objective of this study is to assess supplement utilization patterns and fatty acid and brain-derived neurotrophic factor (BDNF) concentrations in the breast milk of women following vegan, vegetarian, and omnivore diet patterns. METHODS This is a cross-sectional, observational study of 74 lactating women in the United States following a vegan (n = 26), vegetarian (n = 22), or omnivore (n = 26) diet pattern. A single breast milk sample was collected from each participant and assessed for fatty acids and BDNF. RESULTS Median unsaturated fatty acids in the breast milk of vegan, vegetarian, and omnivores, as a percentage of total fatty acids, was 66.0, 57.8, and 56.2%, respectively (p < 0.001). Total omega-3 percentages were 2.29% for vegans, 1.55% for vegetarians, and 1.46% for omnivores (p < 0.001). Docosahexaenoic acid percentages were not different by diet pattern, but over 80% of participants had milk concentrations below 0.30% of total fatty acids. Reports of omega-3 supplements use (10/74) and weekly seafood consumption (3/74) were limited. BDNF was not detectable in any samples. CONCLUSIONS Breast milk from vegans had significantly higher unsaturated fat and total omega-3 fats, and lower saturated fats, trans fats, and omega-6 to omega-3 ratios than their vegetarian and omnivore counterparts. Docosahexaenoic acid concentrations in breast milk were low regardless of maternal diet pattern, and were reflective of low seafood intake and supplement use.
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9.
The Effects of Mold-Fermented Cheese on Brain-Derived Neurotrophic Factor in Community-Dwelling Older Japanese Women With Mild Cognitive Impairment: A Randomized, Controlled, Crossover Trial.
Suzuki, T, Kojima, N, Osuka, Y, Tokui, Y, Takasugi, S, Kawashima, A, Yamaji, T, Hosoi, E, Won, CW, Kim, H
Journal of the American Medical Directors Association. 2019;(12):1509-1514.e2
Abstract
OBJECTIVES To investigate the effects of mold-fermented cheese (MFC) on brain-derived neurotrophic factor (BDNF) in community-dwelling older Japanese women with mild cognitive impairment (MCI). DESIGN Randomized controlled crossover trial. INTERVENTION Participants were randomly assigned to 2 groups. The MFC group was provided with 33.4 g MFC (camembert cheese) daily for 3 months, and the non-MFC group was provided with the same amount of non-MFC (processed cheese made from mozzarella cheese and cream cheese) for 3 months. After the post-intervention analysis (primary analysis), there was a 3-month washout period, followed by a crossover period (secondary analysis). SETTING AND PARTICIPANTS Urban community in Tokyo, Japan. A total of 71 older women aged ≥70 years with MCI based on selected criteria in 689 community-dwelling women. MEASURES Face-to-face interviews were conducted to administer the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) and collect data on medical history. Physical function measures included grip strength, knee extension strength, and usual walking speed. Blood samples were obtained to determine the levels of albumin, vitamin D, high-sensitivity C-reactive protein, and BDNF. RESULTS Significant interactions were observed in BDNF after intervention of MFC intake in the secondary (F = 5.368, P = .024) and combined analyses (F = 4.354, P = .039) but not the primary analysis. There were no significant changes in the 3 categories of MMSE score (normal, MCI, moderate or severe cognitive impairment), GDS score, physical function, and blood indicators. CONCLUSIONS AND IMPLICATIONS Three months of MFC ingestion had beneficial effects on BDNF levels in community-dwelling older women with MCI; however, the BDNF increases did not translate into MMSE scores. Further study into the effects of interventions on cognitive function and depression in older people with MCI is necessary.
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10.
Exercise intensity affects acute neurotrophic and neurophysiological responses poststroke.
Boyne, P, Meyrose, C, Westover, J, Whitesel, D, Hatter, K, Reisman, DS, Cunningham, D, Carl, D, Jansen, C, Khoury, JC, et al
Journal of applied physiology (Bethesda, Md. : 1985). 2019;(2):431-443
Abstract
Aerobic exercise may acutely prime the brain to be more responsive to rehabilitation, thus facilitating neurologic recovery from conditions like stroke. This aerobic priming effect could occur through multiple mechanisms, including upregulation of circulating brain-derived neurotrophic factor (BDNF), increased corticospinal excitability, and decreased intracortical inhibition. However, optimal exercise parameters for targeting these mechanisms are poorly understood. This study tested the effects of exercise intensity on acute BDNF and neurophysiological responses. Sixteen ambulatory persons >6 mo poststroke performed three different 20-min exercise protocols in random order, approximately 1 wk apart, including the following: 1) treadmill high-intensity interval training (HIT-treadmill); 2) seated-stepper HIT (HIT-stepper); and 3) treadmill moderate-intensity continuous exercise (MCT-treadmill). Serum BDNF and transcranial magnetic stimulation measures of paretic lower limb excitability and inhibition were assessed at multiple time points during each session. Compared with MCT-treadmill, HIT-treadmill elicited significantly greater acute increases in circulating BDNF and corticospinal excitability. HIT-stepper initially showed BDNF responses similar to HIT-treadmill but was no longer significantly different from MCT-treadmill after decreasing the intensity in reaction to two hypotensive events. Additional regression analyses showed that an intensity sufficient to accumulate blood lactate appeared to be important for eliciting BDNF responses, that the interval training approach may have facilitated the corticospinal excitability increases, and that the circulating BDNF response was (negatively) related to intracortical inhibition. These findings further elucidate neurologic mechanisms of aerobic exercise and inform selection of optimal exercise-dosing parameters for enhancing acute neurologic effects. NEW & NOTEWORTHY Acute exercise-related increases in circulating BDNF and corticospinal excitability are thought to prime the brain for learning. Our data suggest that these responses can be obtained among persons with stroke using short-interval treadmill high-intensity interval training, that a vigorous aerobic intensity sufficient to generate lactate accumulation is needed to increase BDNF, that interval training facilitates increases in paretic quadriceps corticospinal excitability, and that greater BDNF response is associated with lesser intracortical inhibition response.