Elevated Peripheral Brain-Derived Neurotrophic Factor Level Associated With Decreasing Insulin Secretion May Forecast Memory Dysfunction in Patients With Long-Term Type 2 Diabetes

BackgroundWith the progressive course of diabetes and the decline in islet function, the cognitive dysfunction of patients aggravated.ObjectiveWe aimed to investigate the roles of brain-derived neurotrophic factor (BDNF) and the Val66Met polymorphism in mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 169 Chinese patients with T2DM were involved and divided into long-term (diabetes duration >10 years) and short-term (diabetes duration ≤10 years) diabetes, and in each group, the patients were separated as MCI and the control. Demographic characteristics, clinical variables, and cognitive performances were assessed. The plasma BDNF level was measured via enzyme-linked immunosorbent assay. The Val66Met polymorphisms were analyzed.ResultsLong-term T2DM have lower 2 h postprandial C-peptide (p < 0.05). The BDNF level was slightly higher in patients with MCI than in the controls in each duration group without statistical significance. The relationship of BDNF to Montreal Cognitive Assessment was not proven either. However, in the long-term diabetes group, BDNF concentration remained as an independent factor of logical memory test (β = −0.27; p < 0.05), and they were negatively correlated (r = −0.267; p = 0.022); BDNF was also negatively correlated with fasting C-peptide (r = −0.260; p = 0.022), 2 h postprandial C-peptide (r = −0.251; p = 0.028), and homeostasis model assessment of insulin resistance (r = −0.312; p = 0.006). In genotypic groups, BDNF Val/Val performed better in logical memory test than Met/Met and Val/Met.ConclusionElevated peripheral BDNF level associated with declined islet function, when combined with its Val66Met polymorphism, may forecast memory dysfunction in patients with long-term T2DM.

A Systematic Review of the Effects of Football Playing on Changes in Serum Brain-Derived Neurotrophic Factor Level

Background: Consistent evidence suggests that exercise improves cognition and decision making, with preliminary evidence suggesting that brain-derived neurotrophic factors (BDNFs) may mediate these effects on high-intensity interval activities, such as in football playing. We conducted a systematic review of studies on football players or football task interventions that evaluated the causality of exercise or its relationship with changes in the basal BDNF level. Methods: The search was conducted in PubMed, SPORTDiscus, Cochrane, and FECYT (Web of Sciences, CCC, DIIDW, KJD, MEDLINE, RSCI, and SCIELO) according to the guidelines for performing systematic reviews in the sport sciences field. Results: From the 44 studies initially identified, seven studies were fully reviewed, and their outcome measures were extracted and analysed. In the scientific study of football, the studies published thus far have explored the relationship of serum BDNF levels and other cognitive function factors with the genetic expression of polymorphisms, the anthropometric and fitness conditions, the acute exercise effect of the match, and the typical actions of the match such as heading. Conclusions: The heterogeneity of designs and variables evaluated in studies related to BDNF exercise or interaction and football playing does not allow us to conclusively determine that there is a relationship with the cause or effect of genetic, anthropometric, or conditional factors that derive from an increase in BDNF due to actions during the playing of football.

Reduced BDNF Expression in Auditory Cortex Contributed to Neonatal Pain Induced Hearing Impairment and Dendritic Pruning Deficiency in Mice

Hearing loss in children is common especially in NICU with consequences of worse outcomes in speech, language, education, social functioning, cognitive abilities, and quality of life. Whether neonatal pain is link to increase risks for hearing loss remains to be explored. Here, we implemented Complete Freund's adjuvant (CFA) plantar injection and needle prick model to mimic neonatal pain in NICU during critical period of hearing development. Auditory brainstem response (ABR) test was used to determine the hearing threshold at 4w and 8w postnatal. Sufentanil and Oxycodone were used as analgesic to treat neonatal pain. Hair cell and ribbon synapse stanning were performed to detect cochlear function. Golgi-cox staining and BDNF immunofluorescence of auditory cortex were performed to determine dendritic spine pruning in auditory cortex. The dendritic pruning related protein CaMKII and Rac1/2 level were detected by western blot. We found that CFA induced neonatal pain and ABR threshold increased at 4w and 8w postnatal and the impairment were attenuated after analgesic administration. Neither the inner hair cell (IHC) nor the synapse of CFA mice was damaged in cochlear. CFA mice showed increased dendritic spine density at auditory cortex and reduced BDNF level. Furthermore, Rac1/2 and CaMKII might contributed to the disrupt dendritic spine pruning. Our study suggested that neonatal pain could induced hearing impairment in adulthood ascribed to the reduced BDNF level and AC dendritic spine pruning deficiency, optimal analgesic in early-life could beneficial for hearing development.

Plasma BDNF and Cytokines Correlated with Protein Biomarkers for Bipolar II Disorder

We have previously identified five candidate proteins (matrix metallopeptidase 9 (MMP9), phenylalanyl-TRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin Type 9 (PCSK9)) as potential biomarkers for bipolar II disorder (BD-II). These candidate proteins have been associated with neuroprotective factors (BDNF) and inflammatory factors (cytokines, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α)). However, the correlations between these proteins with plasma BDNF and inflammatory factors remain unknown. We recruited a total of 185 patients with BD-II and 186 healthy controls. Plasma levels of candidate proteins, BDNF, cytokines (TNF-α, CRP, and interleukin-8 (IL-8)) were assessed from each participant. The correlations between levels of candidate proteins, BDNF, and cytokines were analyzed. In the BD-II group, we found that the level of FARSB was positively correlated with the BDNF level (r = 0.397, p < 0.001) and IL-8 (r = 0.320, p < 0.001). The CA-1 level positively correlated with IL-8 (r = 0.318, p < 0.001). In the control group, we found that the FARSB level positively correlated with the BDNF level (r = 0.648, p < 0.001). The CA-1 level positively correlated with TNF-α (r = 0.231, p = 0.002), while the MMP-9 level positively correlated with the CRP level (r = 0.227, p = 0.002). Our results may help in clarifying the underlying mechanism of these candidate proteins for BD-II.

The Utility of BDNF Detection in Assessing Severity of Huntington’s Disease

Brain-derived neurotrophic factor (BDNF) is involved in the survival and maturation of neurons, and also promotes and controls neurogenesis. Its levels are lowered in many neurodegenerative diseases, including Huntington’s disease (HD). Clinical pictures of HD can be very diverse, which makes it difficult to assess its severity; however, molecular markers may be helpful. The aim of the study was to determine the relationship between HD severity and the plasma BDNF concentration in HD patients. The study recruited 42 patients with diagnosed and genetically confirmed HD and 40 healthy volunteers. BDNF levels were determined in plasma with the enzyme-linked immunosorbent assay (ELISA). Correlations between BDNF levels and clinical profiles and HD severity were also investigated. The BDNF level was significantly lower in HD patients compared to the control. There was no correlation between the BDNF level and motor symptoms and cognitive impairment. In the early disease stages, BDNF levels were associated with a better neurological examination, independence, and functional evaluation, in contrast to later HD stages, where the correlations were inverse. Multidirectional correlations between parameters of saccadic disorders and the BDNF level do not allow for drawing a conclusion, whether or not there is a relationship between the severity of saccadic disorders and the BDNF concentration.

The effect of ethanol extract of pasak bumi (Eurycoma longifolia Jack.) on neurogenesis and neuroinflammation of rat post protein malnutrition

Protein malnutrition may affect changes in morphology, neurochemistry, neurogenesis and immune system in the brain. Pasak bumi is often used as an aphrodisiac which is almost the same as Ginseng. The neurogenesis development can be stimulated by ginseng extract intervention. This study aimed to prove the effect of pasak bumi on neurogenesis and neuroinflammation in post-protein malnutrition rats. Experimental research design, rats were divided into 6 groups: KN=normal rats+standard feed, P1=malnutrition rats+aquadest, P2=malnutrition rats + 70% ethanol extract of pasak bumi (EPB) 7.5 mg/kg BW, P3=malnutrition rats + EPB 15 mg/kg BW, P4=malnutrition rats + EPB 22.5 mg/kg BW, P5=malnutrition rats + EPB 30 mg/kg BW. EPB administration for 5 weeks. Parameters examined were levels of BDNF, IL6, TNFα, and serotonin by ELISA method. Statistical analysis using ANOVA and Kruskal Wallis test with 95% confidence level. The results of the study: the mean BDNF level in the P3 group was significantly highest (p=0.047). However, there was no significant difference between groups in IL6, TNFα, and serotonin. Conclusion: The 70% ethanol extract of pasak bumi did not affect neuroinflammation and brain serotonin levels in post-malnutrition rats, but increased BDNF levels in post-malnourished rats at a dose of 22.5 mg/kg BW.

Assessment of serum BDNF levels in complex rehabilitation of patients with ischemic stroke using traditional approaches to the restoration of motor functions

Aim. To assess the relationship between changes in serum brain-derived neurotrophic factor (BDNF) level, regression of motor deficiency, and restoration of functional activity in patients with ischemic stroke after stage II of medical rehabilitation.Materials and methods. The study included 49 patients with ischemic stroke in the middle cerebral artery after stage I of medical rehabilitation. Group I (n = 32) went through stage II of rehabilitation in the early recovery period, group II (n = 17) was discharged for outpatient monitoring at the place of residence. Observation points: day 14 and day 90. Evaluation scales: National Institute of Health Stroke Scale (NIHSS), Fugle – Meyer Scale (FMA), Modified Rankin Scale (mRS). Serum BDNF levels were determined using a MAGPIX multiplex analyzer (Luminex, USA).Results. A comparative analysis of the studied population showed that patients who underwent motor rehabilitation in the early recovery period had greater regression of neurologic deficit according to the ΔNIHSS scale (pgr.I–II = 0.043), a more pronounced increase in the functional activity on the ΔmRS scale (pgr.I–II = 0.047), and positive dynamics according to the FMA scale (pday14–90 = 0.003) in comparison with patients who received outpatient follow-up. The concentration of BDNF was significantly reduced by the end of the early recovery in the group II (pday14–90_gr.II = 0.002). On the contrary, there was no decrease in the level of the BDNF (pday14–90_gr.I = 0.613) in the group of patients undergoing rehabilitation.Conclusion. The results of the study demonstrated the clinical effectiveness of stage II of the comprehensive rehabilitation of patients in the early period of stroke recovery. We can suggest that the success of neurorehabilitation is closely associated with an increase of the BDNF level against the background of its performance. This makes BDNF a potential marker of evaluating the effectiveness of ongoing rehabilitation treatment.

The association between BDNF levels and risperidone-induced weight gain is dependent on the BDNF Val66Met polymorphism in antipsychotic-naive first episode schizophrenia patients: a 12-week prospective study

A growing number of studies have shown that brain-derived neurotrophic factor (BDNF) is associated with weight gain during antipsychotic treatment in schizophrenia patients. However, there is still a lack of research results in the initial stage of antipsychotic treatment. This study aimed to evaluate the relationship between weight gain caused by risperidone monotherapy for 12 weeks and BDNF level in antipsychotic-naive and first-episode (ANFE) patients with schizophrenia, and we hypothesize that this may depend on BDNF Val66Met gene polymorphism. In a 12-week longitudinal trial, 225 ANFE patients were enrolled and treated with risperidone. Body weight was measured at baseline and during the 12-week follow-up. After treatment, the average weight of ANFE patients increased by 2.6 kg. Furthermore, we found that in patients with Val/Val genotype, the increase in serum BDNF levels was negatively correlated with risperidone-induced weight gain (r = −0.44, p = 0.008). Regression analysis showed that the baseline BDNF level was a predictor of weight gain after treatment (β = −0.45, t = −3.0, p = 0.005). Our results suggest that the BDNF signaling may be involved in weight gain caused by risperidone treatment. Furthermore, the negative association between weight gain and increased BDNF levels during risperidone treatment in ANFE schizophrenia depends on the BDNF Val66Met polymorphism.

Association between Serum Brain-derived Neurotrophic Factor and 25-OH Vitamin D Levels with Vitamin D Receptors Gene Polymorphism (rs2228570) in Patients with Autoimmune Thyroiditis and Hypothyroidism

BACKGROUND: Different polymorphisms in Vitamin D receptors (VDRs) have an important role in autoimmune thyroiditis (AIT) risk. Hashimoto’s thyroiditis (HT) is the most recurrent autoimmune thyroid disorder. Patients with HT may suffer from cognitive impairment brain-derived neurotrophic factor (BDNF) which has been identified as an important growth factor that is involved in learning and memory. AIM: This study examined the linkage of VDR gene polymorphism (rs2228570) with blood serum levels of BDNF and 25-OH Vitamin D in thyroid pathology of patients in the West Ukrainian population. METHODS: This research is a case–control study was performed in HSEEU “Bukovinian State Medical University,” Chernivtsi Regional Endocrinology Center, and I. Horbachevsky Ternopil National Medical University, Ukraine, from September 2017 to December 2020. The study involved a total of 153 patients with post-operative hypothyroidism, hypothyroidism induced by AIT, and patients with both AIT and elevated serum antibodies anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay (ELISA) with highly sensitive Human BDNF ELISA Kit. Genotyping of the VDR (rs2228570) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™ Real-Time Polymerase Chain Reaction (PCR) Detection System (Bio-Rad Laboratories, Inc., USA). PCR for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA). RESULTS: Our study revealed a significant decrease in the BDNF level in the study group in carriers of the AA and AG genotypes by 1.58 and 2.39 times, corresponding, compared with carriers of the AA genotype in the control group. Concurrently, there was no significant difference in the BDNF level between different genotypes of VDR rs2228570 in the research group. In our study, analysis of the correlation between serum BDNF levels and 25-OH Vitamin D concentration shows a moderate direct relationship (r = 0.4) between BDNF and 25-OH Vitamin D (p = 0.006). CONCLUSIONS: The rs2228570 VDR polymorphism is not a risk factor for decreased serum BDNF levels. At the same time, our study found a moderate direct relationship between serum BDNF levels and 25-OH Vitamin D.

Hotair and Malat1 Long Noncoding RNAs regulate Bdnf Expression and Oligodendrocyte Precursor Cells Differentiation

BDNF has remarkable protective roles in the central nervous system to ensure neurons and glial cell survival and proper functions. The regulatory processes behind the BDNF expression have not been revealed completely. Here, it was explored whether Malat1 and Hotair lncRNAs play roles in the regulation of Bdnf expression level, modification of fingolimod downstream pathway, and oligodendrocytes precursor cells maturation. By Hotair and Malat1 downregulation, their regulatory mechanism on Bdnf expression was investigated. Immunostaining and RT-qPCR assays were employed to assess the effects of fingolimod and lncRNAs on OPCs maturation. The results represented that Hotair and Malat1 lncRNAs may regulate Bdnf expression in primary glial cells significantly, and also can coordinate fingolimod stimulatory effect on Bdnf expression. Furthermore, Malat1 may have a role in the last stages of the intrinsic oligodendrocyte myelination. Here it was demonstrated that these lncRNAs have critical roles in the Bdnf level, fingolimod mechanism of action, and OPCs maturation. Understanding the regulatory mechanism of neurotrophins leads to a better comprehension of the pathogenesis of the neurodegenerative disorder and designing more effective treatments.