Brain-derived Neurotrophic Factor Concentrations Research Articles

Smoking-Dependent Association of Serum Brain-Derived Neurotrophic Factor with Pulmonary Function Parameters in Chronic Obstructive Pulmonary Disease.

Background and Objectives: One of the members of the neurotrophin (NT) family is the brain-derived neurotrophic factor (BDNF). In addition to its role in the nerve system, it has been found to play a role in lung health and diseases. Materials and Methods: The serum concentrations of BDNF were assessed in 57 patients with COPD and in 19 control individuals and the possible associations of BDNF with the spirometric indexes and disease stages were explored. Results: We did not find a significant difference between the serum concentrations of BDNF of patients and controls (p = 0.521). A significant negative correlation of the serum BDNF levels with the age of the patients (Rho = -0.279, p = 0.036) was observed. In addition, a borderline negative correlation with the age of disease onset (Rho= -0.244, p = 0.063) was also found. When analyzing these correlations in different genders, we found stronger statistical significance in male patients (Rho = -0.398, p = 0.009; and Rho = -0.419, p = 0.006), while no such significance was found in females (p = 0.574 and p = 0.342). The analyses of the possible relations of serum BDNF concentration with the spirometric parameters in the whole group of patients did not reveal any significance (p = 0.231 for FEV1%pr. and p = 0.271 for FEV1/FVC%). However, when the patients were dichotomized on the basis of smoking habits, we obtained a strong positive correlation between BDNF and FEV1%pr. (Rho = 0.501, p = 0.048) in non-smokers, but strong negative correlations with FEV1%pr. (Rho = -0.468, p = 0.003) and with FEV1/FVC% (Rho = -0.331, p = 0.040) in ex/current smokers. Non-smokers with moderate disease (GOLD II) had higher BDNF serum concentrations than patients with GOLD stage III/IV (p = 0.031). In ex/current smokers, there was an opposite association (p = 0.045). Conclusions: The results of our study suggest that the expression and secretion of BDNF are changed in COPD, but its effects and functions may differ according to the smoking history of the patients.

The effects of PPARγ agonists on long‑termpotentiation and apoptosis in the hippocampusarea of juvenile hypothyroid rats.

The aim of the present study was to evaluate the effect of rosiglitazone (RSG) or pioglitazone (POG) on the synaptic plasticity, neuronal apoptosis, brain-derived neurotrophic factor (BDNF), and nitric oxide (NO) metabolites in the hippocampus of juvenile hypothyroid rats. The animals were divided into four groups: control; propylthiouracil (PTU), 0.05% dose in drinking water for 42 days; PTU-POG; and PTU-RSG. The POG (20 mg/kg) and the RSG (4 mg/kg) were administered by IP injection. We conducted long‑term potentiation (LTP) in the cornu ammonis 1 area of the hippocampus using high‑frequency stimulation of the Schaffer collateral pathway. Then, the hippocampal tissues were collected to determine BDNF and NO levels and the degree of apoptosis. PTU administration decreased the slope (10-90%) and amplitude of the fEPSPs compared to control. Injection of RSG or POG increased the slope, slope (10-90%), and amplitude of the fEPSP in the PTU‑POG or PTU‑RSG groups compared to the PTU group. TUNEL‑positive neurons and NO metabolites in the hippocampus of the PTU group were higher than those of the control group. RSG or POG increased BDNF content in PTU-POG or PTU-RSG groups. Treatment of the rats with POG or RSG decreased apoptotic neurons and NO metabolites in the hippocampus of PTU-POG or PTU-RSG groups, respectively, compared to the PTU group. This study's results revealed that POG or RSG normalized LTP impairment, neuronal apoptosis, and improved BDNF content in the hippocampal tissue of juvenile hypothyroid rats.

Cognitive functions and the brain-derived neurotrophic factor in patients with mild autonomous cortisol secretion.

The impact of abnormal cortisol secretion on cognitive functions in patients with mild autonomous cortisol secretion (MACS) remains uncertain. To assess cognitive functions, determine serum brain-derived neurotrophic factor (BDNF) concentration in patients with MACS, and investigate the association between cognitive subdomains and BDNF. We prospectively recruited 84 participants-28 patients with MACS, 28 patients with nonfunctional adrenal adenoma (NFAA), and 28 control subjects matched for age, gender, body mass index (BMI), visceral adiposity, and educational level. The serum BDNF concentration of participants was measured. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-focused interviews and Montreal Cognitive Assessments (MoCA) were carried out by an experienced psychiatrist. Patients with MACS had a higher serum BDNF concentration than the NFAA (P = .001), while that of patients with NFAA was lower than the controls (P = .044). Linear regression analysis revealed BMI and morning cortisol after overnight 1 mg dexamethasone (DST) were mostly associated with BDNF (P < .05). No significant difference was found in MoCA scores between MACS and NFAA groups (P = .967), whereas those were lower than the control group (P = .004). When the cognitive subdomains were examined separately, MACS group performed higher memory score than NFAA (P = .045), but lower language scores than both the NFAA (P = .024) and control groups (P < .001). In the whole group, BDNF concentration was positively correlated with memory score (r = 0.337, P = .002), whereas DST was negatively correlated with language score (r = -0.355, P = .008). Low-grade hypercortisolism is associated with elevated BDNF concentrations, which may be a protective factor for memory function in patients with MACS relative to those with NFAA.

Oral administration of liposome-encapsulated thymol could alleviate the inflammatory parameters in serum and hippocampus in a rat model of Alzheimer's disease

BackgroundNeuroinflammation is closely related to Alzheimer's Disease (AD) pathology, hence supplements with anti-inflammatory property could help attenuate the progression of AD. This study was conducted to evaluate the potential anti-inflammatory effects of liposome encapsulated thymol (LET), administered orally, in prevention of Alzheimer in a rat model by anti-inflammatory mechanisms. MethodsThe rats were grouped into six groups (n = 10 animals per group), including Control healthy (Con), Alzheimer's disease (AD) model, AD model treated with free thymol in 40 and 80 mg/kg body weight (TH40 and TH80), AD model treated with LET in 40 and 80 mg/kg of body weight (LET40 and LET80). The behavioral response of step through latency (Passive Avoidance Test), concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) were assessed in serum and hippocampus. ResultsThe results showed that significant increase in concentrations of IL-1β (P = 0.001), IL-6 (P = 0.001), TNF-α (P = 0.001) and COX-2 (P = 0.001) in AD group compared with healthy control rats. AD induction significantly reduced step through latency and revealed deficits in passive avoidance performance. The results also showed the treatment with free thymol especially in higher concentrations and also LTE could decrease serum concentrations of IL-1β (P < 0.05), IL-6 (P < 0.05), TNF-α (P < 0.05), and COX-2 (P < 0.05) and increase BDNF (P < 0.05) compared with control Alzheimer rats in hippocampus and serum. There were also significant correlations between serum and hippocampus concentrations of IL-1β (r2 = 0.369, P = 0.001), IL-6 (r2 = 0.386, P = 0.001), TNF-α (r2 = 0.412, P = 0.001), and COX-2 (r2 = 0.357, P = 0.001). It means a closed and positive relation between serum and hippocampus concentrations of IL-1β, IL-6, TNF-α, and COX-2. ConclusionsLET demonstrates its ability to attenuate neuroinflammatory reaction in AD model through suppression of IL-1β, IL-6, and TNF-α and COX-2 indicators. Hence, it can ameliorate AD pathogenesis by declining inflammatory reaction.

Plasma BDNF/Irisin Ratio Associates with Cognitive Function in Older People.

Reliable blood biomarkers are crucial for early detection and treatment evaluation of cognitive impairment, including Alzheimer's disease and other dementias. To examine whether plasma biomarkers and their combination are different between older people with mild cognitive impairment (MCI) and cognitively normal individuals, and to explore their relations with cognitive performance. This cross-sectional study included 250 older adults, including 124 participants with MCI, and 126 cognitively normal participants. Plasma brain-derived neurotrophic factor (BDNF), irisin and clusterin were measured, and BDNF/irisin ratio was calculated. Global cognition was evaluated by the Montreal Cognitive Assessment. Plasma irisin levels, but not BDNF, were significantly different between MCI group and cognitively normal group. Higher irisin concentration was associated with an increased probability for MCI both before and after controlling covariates. By contrast, plasma BDNF concentration, but not irisin, was linearly correlated with cognitive performance after adjusting for covariates. Higher BDNF/irisin ratios were not only correlated with better cognitive performance, but also associated with lower risks of MCI, no matter whether we adjusted for covariates. Plasma BDNF and irisin concentrations increased with aging, whereas BDNF/irisin ratios remained stable. No significant results of clusterin were observed. Plasma BDNF/irisin ratio may be a reliable indicator which not only reflects the odds of the presence of MCI but also directly associates with cognitive performance.

An Examination into the Effects of a Nutraceutical Supplement on Cognition, Stress, Eye Health, and Skin Satisfaction in Adults with Self-Reported Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Dietary quality and the consumption of antioxidant-rich foods have been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: Compared to the placebo, nutritional supplementation was associated with larger improvements in one primary outcome measure comprising episodic memory (p = 0.037), but not for working memory (p = 0.418) or verbal learning (p = 0.841). Findings from secondary and exploratory outcomes demonstrated that the nutraceutical intake was associated with larger improvements in the Everyday Memory Questionnaire (p = 0.022), increased plasma brain-derived neurotrophic factor (p = 0.030), decreased plasma malondialdehyde (p = 0.040), and increased skin carotenoid concentrations (p = 0.006). However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

Penehyclidine hydrochloride improves cognitive function of rats with brain injury via CAMP/CREB signaling pathway.

This study explored the impact of penehyclidine hydrochloride on cognitive function in rats with brain injury. Sprague-Dawley rats (n=36) were randomly assigned to sham-operation, model, and penehyclidine hydrochloride groups. Rats in the sham-operation group underwent craniotomy, while the model and penehyclidine hydrochloride groups received brain injury models and interventions with normal saline and penehyclidine hydrochloride, respectively. Specimens were obtained two weeks post-intervention. Neurological deficits were evaluated using Zea-Longa scores, and memory was assessed with the Morris water maze test. ELISA determined brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) content. mRNA expressions of BDNF and NGF were assessed via qPCR, and phosphorylated CREB (p-CREB) protein expression was measured by Western blotting. Compared to the sham-operation group, both model and penehyclidine hydrochloride groups showed increased Zea-Longa scores. Escape latencies were longer and platform crossings were fewer in model and penehyclidine hydrochloride groups compared to the sham-operation group, but penehyclidine hydrochloride demonstrated a shorter latency and more platform crossings than the model group. BDNF and NGF content decreased in model and penehyclidine hydrochloride groups compared to the sham-operation group, with an increase in the penehyclidine hydrochloride group compared to the model group. mRNA expression levels declined in model and penehyclidine hydrochloride groups but were higher in the latter. p-CREB protein expression was lower in model and penehyclidine hydrochloride groups compared to the sham-operation group but higher in the penehyclidine hydrochloride group than the model group. Penehyclidine hydrochloride exhibited neuroprotective effects by upregulating the cAMP/CREB signaling pathway, improving cognitive function in rats with brain injury.

Does brain-derived neurotrophic factor play a role in the association between maternal prenatal mental health and neurodevelopment in 2-year-old children?

ObjectiveTo evaluate the role of brain-derived neurotrophic factor (BDNF)—a crucial modulator of neural development and plasticity—in the association between prenatal maternal anxiety, depression, and perceived stress and child neurodevelopment in a prospective cohort study. MethodsWe included 526 eligible mother-child pairs from the Shanghai Birth Cohort in the study. Maternal mental health was assessed at mid-pregnancy using Zung's Self-Rating Anxiety Scale, Center for Epidemiologic Studies Depression Scale, and Perceived Stress Scale. The concentration of BDNF in cord blood was measured by ELISA. The offspring neurodevelopment at 24 months of age was assessed using the Bayley Scales. Linear and non-linear regression models were used. ResultsThe average cord blood BDNF levels were higher in female newborns and those born via vaginal delivery, full term, and normal birth weight. Prenatal maternal anxiety (β = −0.32; 95 % CI: −0.55, −0.09), depression (β = −0.30; 95 % CI: −0.52, −0.08), and perceived stress (β = −0.41; 95 % CI: −0.71, −0.12) scores were negatively associated with social-emotional performance at 24 months of age. However, no significant associations were found between prenatal maternal anxiety, depression, or perceived stress at mid-pregnancy and cord blood BDNF levels, as well as between cord blood BDNF levels and child neurodevelopment. LimitationsMaternal mental health at different timepoints during pregnancy and generalizability of the results warrant further assessment. ConclusionsPrenatal mental health was not associated with cord blood BDNF level and that BDNF may not be a mediator in the association between prenatal mental health and child neurodevelopment.

Long-term effects of an egg-protein hydrolysate on cognitive performance and brain vascular function: a double-blind randomized controlled trial in adults with elevated subjective cognitive failures

PurposeShort-term intake of the egg-protein hydrolysate Newtricious (NWT)-03 improved executive function, but underlying mechanisms and long-term effects, including other cognitive domains, are unknown.MethodsA 36-week randomized controlled trial involving 44 overweight/obese individuals experiencing elevated Subjective Cognitive Failures (SCF; aged 60–75 years) assessed the impact of daily consumption of 5.7 g of NWT-03 or placebo powders on cognitive performance (psychomotor speed, executive function, memory) and Cerebral Blood Flow (CBF), a marker of brain vascular function. Cognitive performance was evaluated using a neurophysiological test battery (CANTAB) and CBF was measured using magnetic resonance imaging perfusion method Arterial Spin Labeling (ASL). Serum samples were collected to determine brain-derived neurotrophic factor (BDNF) concentrations.ResultsAnthropometrics, and energy and nutrient intakes remained stable throughout the trial. NWT-03 was well tolerated, and compliance was excellent (median: 99%; range: 87–103%). No overall intervention effects were observed on cognitive performance or CBF, but post-hoc analyses revealed significant improvements on executive function in women, but not men. Specifically, a reduction of 74 ms in reaction latency on the multitasking task (95% CI: −134 to −15; p = 0.02), a reduction of 9 between errors (95%CI: −14 to −3; p < 0.001), and a reduction of 9 total errors (95%CI: −15 to −3; p < 0.001) on the spatial working memory task were found in women. No intervention effects were observed on serum BDNF concentrations (p = 0.31).ConclusionLong-term consumption of NWT-03 improved multitasking abilities and working memory in women with elevated SCF. Brain vascular function remained unaffected. Sex differences in executive function require additional clarification.

Effects of antidepressant and antipsychotic medication on peripheral brain-derived neurotrophic factor concentration: Systematic review and meta-analysis

Brain-derived neurotrophic factor (BDNF) is an important regulatory protein in the pathophysiology of psychiatric disorders. Several studies have reported the relationship between peripheral BDNF concentrations and the use of psychoactive drugs. However, the results remain controversial. This study aimed to evaluate the effects of psychoactive drugs on BDNF concentrations and to explore the association between changes in BDNF concentrations and improvements in clinical scores. A systematic review and meta-analysis were conducted. Six electronic databases, including PubMed, Scopus, Medline, Web of Science, Google Scholar and Science Direct, were searched. Changes in BDNF concentrations were compared before and after psychoactive treatment, using the standardized mean difference (SMD) and 95 % confidence interval (95 % CI). Twenty-three studies were included. A significant increase in serum BDNF concentrations was observed after treatment with antipsychotics (SMD=0.43; 95 %CI: 0.26, 0.60) and antidepressants (SMD=0.49; 95 %CI: 0.23, 0.74). However, the plasma BDNF concentration was not affected by antidepressant and antipsychotic medication. Although an improvement in clinical scores was observed after treatment, no significant association was observed between changes in BDNF concentrations and the changes in the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAM-D) scores. In conclusion, antidepressants and antipsychotics increase serum BDNF concentrations.

Effect of Glycemic Disorders and Habits on the Concentration of Selected Neurotrophic Factors in Patients with Lumbosacral Intervertebral Disc Degeneration.

Unhealthy habits, such as overeating processed and high-calorie foods, alcohol abuse, and smoking, negatively impact human health. It has been suggested that the inflammatory process and the resulting growth of nerve fibers within the intervertebral disc (IVD) fissures is the main reason for the pain accompanying IVD degeneration (IVDD). The aim of this study was to determine whether smoking, alcohol consumption, overweight/obesity, or diabetes comorbidity contribute to the development of IVDD and how the aforementioned factors affect the levels of brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and growth associated protein 43 (GAP-43) in the study and control groups (intervertebral discs, IVDs from cadavers, and serum samples from voluntary blood donors). The study group comprised 113 patients diagnosed with IVDD who qualified for microdiscectomy. Two control groups (I and II) were used in this study. The first included 81 IVDs obtained from Caucasian human cadavers. Control group II, on the other hand, included serum samples obtained from 113 voluntary blood donors. The expression profiles of BDNF, GDNF, and GAP-43 were determined by enzyme-linked immunosorbent assay (ELISA). Our statistical analysis confirmed that patients who were overweight/obese, smoked tobacco, consumed alcohol, or had diabetes had a higher risk of IVDD (OR > 1). Statistical analysis showed that BDNF, GAP-43, and GDNF concentrations were significantly higher in the IVDs and serum samples obtained from the study group compared to the control group (p < 0.05). In addition, higher levels of BDNF, GDNF, and GAP-43 were noted in IVDD patients who consumed alcohol, smoked tobacco, were overweight/obese, or had comorbid diabetes compared to patients without these risk factors (p < 0.05). We showed that changes in energy metabolism, habits, and lifestyle, as well as the degenerative process of IVD in the lumbosacral spine contribute to changing the concentration profile of the analyzed neurotrophic factors.

A comprehensive assessment of the cholinergic-supporting and cognitive-enhancing effects of Rosa damascena Mill. (Damask rose) essential oil on scopolamine-induced amnestic rats.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues. The control, amnesia (scopolamine, 1mg/kg/i.p.) and treatment (RDEO, 100μL/kg/p.o. or galantamine, 1.5mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor. According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically -citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active-state human M1 mAChR and anchored here chiefly by hydrogen-bonding and alkyl-π interactions. Our findings offer a solid experimental foundation for future RDEO-based medicinal product development for patients suffering from AD.

Relationship between brain-derived neurotrophic factor and mild to moderate cognitive impairment in the older Mexican population

BackgroundMild–moderate cognitive impairment is a frequent pathology in the adult population. It is important to explore early expression biomarkers that contribute to early detection and benefit the prognostic outlook. Brain-derived neurotrophic factor (BDNF) is an essential regulator of synaptic plasticity, neuronal survival, and differentiation, and even a critical molecular target for drug development in neurological disorders. It is crucial to carry out studies in the early stages that better clarify the landscape of BDNF. ObjectiveTo compare the serum levels of BDNF in healthy adult patients and those with mild to moderate cognitive impairment. Materials and methodsA casecontrol study in patients over 55- years with cognitive impairment, obtained by the MMSE® and MoCA® screening scales. A total of 191 patients, 102 patients with cognitive impairment (cases) and 89 healthy ones (controls) participated in the study. Blood samples were collected to obtain serum, with the determination of BDNF concentrations. For differences in BDNF concentrations, a one-way analysis of variance was used. The significance level of p<.05. ResultsThe mean serum concentration of BDNF in the case group was 277.68±75.09 vs. the control group, where the concentration was 354.97±66.06 pg/ml (p=.001). ConclusionsThere is an association between decreased BDNF levels and mild and moderate cognitive impairment in our study population.

Relationship between plasma brain-derived neurotrophic factor levels and neurological disorders: An investigation using Mendelian randomisation

BackgroundAltered brain-derived neurotrophic factor (BDNF) concentrations have been detected in the central nervous system tissues and peripheral blood. These alterations are associated with a series of neurological disorders. ObjectiveTo investigate the potential causal relationships between genetically determined plasma BDNF levels and various neurological diseases using a two-sample Mendelian randomisation study. MethodsWe selected single nucleotide polymorphisms strongly related to plasma BDNF levels as instrumental variables. Within the Mendelian randomisation framework, we used summary-level statistics for exposure (plasma BDNF levels) and outcomes (neurological disorders). ResultsWe observed suggestive evidence of a relation between higher plasma BDNF levels and less risk of nontraumatic intracranial haemorrhage (nITH) (odds ratio [OR] = 0.861, 95 % confidence interval [CI]: 0.774–0.958, P = 0.006, PFDR = 0.078), epilepsy (OR = 0.927, 95 % CI: 0.880–0.976, P = 0.004, PFDR = 0.078), focal epilepsy (OR = 0.928, 95 % CI: 0.874–0.986, P = 0.016, PFDR = 0.139), and non-lesional focal epilepsy (OR = 0.981, 95 % CI: 0.964–0.999, P = 0.041, PFDR = 0.267). Combined with the UK Biobank dataset, the association of plasma BDNF levels with nITH remained significant (OR = 0.88, 95 % CI: 0.81–0.96, P < 0.01). The combined analysis of three consortium datasets demonstrated a considerable impact of plasma BDNF on epilepsy (OR = 0.94, 95 % CI: 0.90–0.98, P < 0.01) and a suggestive impact on focal epilepsy (OR = 0.94, 95 % CI: 0.89–0.99, P = 0.02). However, there was no apparent correlation between plasma BDNF levels and other neurological disorders or related subtypes. ConclusionsOur study supports a possible causal relationship between elevated plasma BDNF levels and a reduced risk of nITH, epilepsy, and focal epilepsy.

Short-term Aronia melanocarpa extract supplementation improves cognitive performance: a randomized, double-blind, placebo-controlled cross-over study in healthy young adults

PurposeEvidence on the potential beneficial effects of anthocyanin-rich foods and supplements on cognitive performance is mainly based on acute or long-term studies in older adults. However, short-term studies focusing on a younger population are lacking. Therefore, short-term effects of Aronia melanocarpa extract (AME) supplementation on cognitive performance were investigated in healthy young adults. Potential underlying mechanisms were also addressed.MethodsA randomized, double-blind, placebo-controlled cross-over study was performed involving 35 apparently healthy young adults. Participants consumed AME (180 mg anthocyanins/day) or a placebo for 1 week, separated by at least 2 weeks of wash-out. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Furthermore, arterial stiffness (carotid-to-femoral pulse wave velocity), retinal microvascular calibers (fundus photography), and serum brain-derived neurotrophic factor (BDNF) concentrations were measured at baseline and after 1 week.ResultsParticipants had a mean age of 25 ± 4 years and an average BMI of 23.4 ± 2.7 kg/m2. Compliance was excellent and the study product was well-tolerated. As compared to placebo, movement time was significantly reduced by 4.8% within the five-choice reaction time test after 1 week of AME supplementation (intervention effect: – 12 ms; p < 0.05). Memory and executive function did however not change. Serum BDNF concentrations were significantly higher after AME supplementation as compared to placebo (+ 5.7%; intervention effect: 1.8 ng/mL; p < 0.05). However, arterial stiffness and retinal microvascular calibers were not affected.ConclusionShort-term AME supplementation beneficially affected cognitive performance as attention and psychomotor speed improved. Serum BDNF concentrations were increased, but vascular function markers were not affected.Clinical trial registrationThe study was registered on Clinical Trials under NCT03793777 on January 4th, 2019.

Dietary intake of methyl donor nutrients in relation to metabolic health status, serum levels of brain-derived neurotrophic factor and adropin

There is a lack of evidence on dietary intake of methyl donor nutrients with metabolic health status and related biomarkers. Thus, this study aimed to assess the relation between methyl donor nutrients intake and metabolic health status with regarding the interactive roles of brain-derived neurotrophic factor (BDNF) and adropin in Iranian adults. This cross-sectional survey was conducted among 527 Iranian adults (45.7% female) selected by multistage cluster random-sampling method. A validated food frequency questionnaire was used to evaluate participants' dietary intake. Metabolic unhealthy status was defined by Wildman criteria as having ≥ 2 of hyperglycemia, hypertriglyceridemia, hypo-HDL-cholesterolemia, hypertension, chronic inflammation, and insulin resistance. Concentrations of metabolic parameters, BDNF and adropin were determined using fasting blood samples. An inverse association was found between methyl donor nutrients intake and metabolically unhealthy status in multivariable-adjusted model (ORT3 vs. T1=0.30; 95%CI: 0.12-0.75). This association was especially significant among overweight/obese adults and was stronger in women. Additionally, consumption of vitamin B6 and choline was separately related to reduced odds of metabolically unhealthy status. Methyl donor intake was not significantly related to low BDNF (ORT3 vs. T1=0.93; 95%CI: 0.60-1.44) and adropin (ORT3 vs. T1=0.71; 95%CI: 0.44-1.15). However, the interaction between high methyl donor nutrients intake and high BDNF was related to lower odds of metabolically unhealthy status in multivariable-adjusted model (ORMDNS∗BDNF=0.27; 95%CI: 0.11-0.67). Higher intake of methyl donor nutrients, alone and in interaction with BDNF levels, was associated with decreased odds of metabolically unhealthy status in Iranian adults.

Early human contact and housing for pigs – part 3: ability to cope with the environment

Early experiences can have long-term impacts on stress adaptability. This paper is the last of three in a series on early experiences and stress in pigs, and reports on the effects of early human contact and housing on the ability of pigs to cope with their general environment. Using a 2 × 2 factorial design, 48 litters of pigs were reared in either a farrowing crate (FC) or a loose farrowing pen (LP; PigSAFE pen) which was larger, more physically complex and allowed the sow to move freely. Piglets were provided with either routine contact from stockpeople (C), or routine contact plus regular opportunities for positive human contact (+HC) involving 5 min of scratching, patting and stroking imposed to the litter 5 days/week from 0 to 4 weeks of age. At 4 weeks of age (preweaning), C piglets that were reared in FC had considerably lower concentrations of serum brain-derived neurotrophic factor (BDNF) than piglets from the other treatment combinations. Compared to C pigs, +HC pigs had fewer injuries at 4 weeks of age. There were no clear effects of human contact on BDNF concentrations or injuries after weaning, or on basal cortisol or immunoglobulin-A concentrations, behavioural time budgets, tear staining, growth, or piglet survival. Compared to FC piglets, LP piglets showed more play behaviour and interactions with the dam and less repetitive nosing towards pen mates during lactation. There was no evidence that early housing affected pigs’ behavioural time budgets or physiology after weaning. Tear staining severity was greater in LP piglets at 4 weeks of age, but this may have been associated with the higher growth rates of LP piglets preweaning. There was no effect of lactation housing on growth after weaning. Preweaning piglet mortality was higher in the loose system. The findings on BDNF concentrations, injuries and play behaviour suggest improved welfare during the treatment period in +HC and LP piglets compared to C and FC piglets, respectively. These results together with those from the other papers in this series indicate that positive human interaction early in life promotes stress adaptability in pigs. Furthermore, while the farrowing crate environment deprives piglets of opportunities for play behaviour and sow interaction, there was no evidence that rearing in crates negatively affected pig welfare or stress resilience after weaning. Whether these findings are specific to the two housing systems studied here, or can be generalised to other housing designs, warrants further research.

Effect of Regular Aerobic Exercise on Cognitive Function, Depression Level and Regulative Role of Neurotrophic Factor: A Prospective Cohort Study in the Young and the Middle-Aged Sample.

Mild cognitive impairment (MCI) and depressive disorder (DD), which are associated with unhealthy lifestyles, are prevalent worldwide. This study aimed to investigate the effects of regular aerobic exercise on cognitive function, depression, and the regulatory role of neurotrophic growth factors for providing scientific basis in preventing MCI and DD in healthy individuals. Eighty members of the fitness center and 80 community residents were recruited, who were administered by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Patient Health Questionnaire (PHQ-9). Brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF) in the peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). The RBANS and other factor scores, except for visuospatial abilities, were higher and PHQ-9 scores were lower in the study group than in the control group. The concentrations of BDNF and GDNF in the study group were higher than those in the control group. RBANS and its factor scores positively and PHQ-9 negatively correlated with BDNF and GDNF levels. Finally, multiple regression analysis showed that BDNF, as a predictor of RBANS, could explain 59.90% of its variance and that GDNF was a predictor of PHQ-9 could explain 12.30% of the variance. Regular aerobic exercise can improve cognitive function and depressive symptoms by increasing the BDNF and GDNF levels.

The relationship between neurotrophins and cognitive functions in the context of emotional response to sleep deprivation

IntroductionStudies conducted up to date on the subject of deprivation of sleep (DS) primarily focused either on its impact on certain cognitive abilities or mood-enhancing effects in patients with depression. A notable body of evidence suggests that both might be related to alterations in neurotrophin synthesis induced by DS. However, the role of NTs as an interface between DS, mood, and cognitive functions is unclear.ObjectivesThe study aimed to investigate associations between cognitive abilities measured by Trail Making Test (TMT) and Stroop Color and Wort Test (ST), serum protein concentrations of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT3), neurotrophin-4 (NT4) as well as the expression of their respective genes after a night of sleep deprivation.MethodsEach participant (n=76) underwent a 24-hour DS under the control of actigraphy. Venous blood collection, TMT, and ST were carried out in the morning after DS. Mood was evaluated twice, after DS and in the preceding evening; based on the alleviation of depression symptoms participants were divided into respondents (RE; n=47) and non-respondents (NR; n=29). Serum protein concentration was determined using ELISA kits. Gene expression was evaluated by quantitative real-time polymerase chain reaction with gene-specific probes (reference gene: β-actin). Relative expression was calculated using the Livak formula. TMT is a neuropsychological instrument; Part 1 is thought to evaluate mostly attention, whereas Part 2 executive functions. ST is a 2-part test applied in the assessment of response inhibition and complex attention.ResultsIn RE, cognitive abilities were not associated with expression levels of any of the studied proteins or mRNA (all p&gt;0.05). In NR, BDNF and GDNF mRNA expressions negatively correlated with TMT Part 1 (p=0.017, p=0.048, respectively); scores obtained in TMT Part 2 bore a similar relation to BDNF, GDNF, and NT4 mRNA (p=0.034, p=0.041, p=0.026, respectively). In this group, expression of all BDNF, GDNF, NT3, NT4 mRNA correlated negatively with both parts of ST (p&lt;0.001, p=0.009, p=0.042, p=0.009 for Part 1; p&lt;0.001, p=0.003, p=0.031, p=0.014 for Part 2, respectively).ConclusionsThose results suggest that alterations in the synthesis of NTs might be an element of the molecular milieu characterizing different types of DS response. Negative correlations between test scores and NT mRNA expressions could imply that the reduction of the production of NT proforms might protect against the decline of cognitive functions in the aftermath of DS. Projects using a larger battery of tests as well as analyzing immature forms of NTs would be desirable in order to further investigate mechanisms underlying DS response.Disclosure of InterestNone Declared

Interactions between neurotrophins, mood, and physical activity under the conditions of sleep deprivation

Sleep deprivation (DS) is the forced elimination of sleep. While brain-derived neurotrophic factor (BDNF) has been extensively studied in the context of in mood changes following DS, the role of other neurotrophins remains elusive. This study explores the impact of DS on BDNF, glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT3), and neurotrophin-4 (NT4) at mRNA and protein level, considering their potential links to mood disturbances. The study involved 81 participants subjected to polysomnography (PSG) and DS. Blood samples, mood assessments, and actigraphy data were collected twice, after PSG and DS. NT mRNA expression and serum protein concentrations of BDNF, GDNF, NT3, and NT4 were measured. Participants were divided into Responders and Non-Responders based on mood improvement after DS. DS reduced BDNF mRNA expression in all participants, with no change in serum BDNF protein. GDNF protein decreased in Non-Responders, while Responders exhibited reduced GDNF mRNA. NT3 protein increased in both groups, while NT3 mRNA decreased in Respondents. NT4 protein rose universally post-DS, but NT4 mRNA remained unchanged. Physical activity (PA) negatively correlated with mRNA expression of BDNF, GDNF, and NT3 post-DS. The study’s short DS duration and exclusion of immature NT forms limit comprehensive insights. GDNF, together with NT3, might play an important role in mood response to DS. PA during DS seems to impair the mRNA expression of NTs in leukocytes. Future studies on the subject of sleep deprivation might consider investigating the relationship between BDNF and NT4 in the context of their apparent redundancy.