Neurotrophic Factor Concentrations Research Articles

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.

Short-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. A 36-week randomized controlled trial involving 44 overweight/obese individuals experiencing elevated Subjective Cognitive Failures (SCF; aged 60-75years) assessed the impact of daily consumption of 5.7g 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. Anthropometrics, 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 74ms 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). Long-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.

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.

Evidence 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. A randomized, double-blind, placebo-controlled cross-over study was performed involving 35 apparently healthy young adults. Participants consumed AME (180mg anthocyanins/day) or a placebo for 1week, separated by at least 2weeks 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 1week. Participants had a mean age of 25 ± 4years and an average BMI of 23.4 ± 2.7kg/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 1week of AME supplementation (intervention effect: -12ms; 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: 1.8ng/mL; p < 0.05). However, arterial stiffness and retinal microvascular calibers were not affected. Short-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. The study was registered on Clinical Trials under NCT03793777 on January 4th, 2019.

Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis.

Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.

The BDNF protein is associated with glucose homeostasis and food intake in carriers of common BDNF gene variants.

The brain-derived neurotrophic factor (BDNF) concentrations may differ between BDNF gene genotype carriers. These changes occur in individuals with metabolic and mental disorders. The aim of this study was to assess the associations of glucose homeostasis parameters and the frequency of food consumption with BDNF protein concentrations based on the BDNF single-nucleotide polymorphisms (SNPs). Among the 439 participants, some common rs10835211 BDNF gene variants were analyzed. We evaluated BDNF concentration, fasting glucose and insulin concentrations and during oral glucose tolerance tests. Anthropometric measurements, body composition, and body fat distribution were assessed, and 3-day food intake diary and food frequency questionnaire were completed. We noticed significant differences in concentration of BDNF between AA and AG genotype rs10835211 carriers (p=0.018). The group of AA genotype holders were older, and positive correlation was found between age and BDNF in the whole study population (p=0.012) and in the GG genotype carriers (p=0.023). Moreover, BDNF protein correlated with fasting insulin (p=0.015), HOMA-IR (p=0.031), HOMA-B (p=0.010) , and the VAT/SAT ratio (p=0.026) in the GG genotype individuals. Presence of the GG genotype was negatively correlated with nut and seed (p=0.047), lean pork consumption (p=0.015) and the BDNF protein. Moreover, we observed correlations between the frequency of chicken (p=0.028), pasta (p=0.033) and sweet food intake (p=0.040) and BDNF concentration in the general population. Among carriers of the AA genotype, we observed a positive correlation between the consumption of rice (p=0.048) and sweet food (p=0.028) and the BDNF protein level. Peripheral BDNF may be associated with visceral fat content and insulin concentrations in the GG genotype carriers and may depend on variable food intake, which warrants further investigation.

An acute bout of resistance exercise increases BDNF in hippocampus and restores the long-term memory of insulin-resistant rats.

A sedentary lifestyle, inadequate diet, and obesity are substantial risk factors for Type 2 diabetes mellitus (T2DM) development. A major picture of T2DM is insulin resistance (IR), which causes many impairments in brain physiology, such as increased proinflammatory state and decreased brain-derived neurotrophic factor (BDNF) concentration, hence reducing cognitive function. Physical exercise is a non-pharmacological tool for managing T2DM/IR and its complications. Thus, this study investigated the effects of IR induction and the acute effects of resistance exercise (RE) on memory, neurotrophic, and inflammatory responses in the hippocampus and prefrontal cortex of insulin-resistant rats. IR was induced by a high-fat diet and fructose-rich beverage. Insulin-resistant rats performed acute resistance exercise (IR.RE; vertical ladder climb at 50-100% of the maximum load) or rest (IR.REST; 20min). Cognitive parameters were assessed by novel object recognition (NOR) tasks, and biochemical analyses were performed to assess BDNF concentrations and inflammatory profile in the hippocampus and prefrontal cortex. Insulin-resistant rats had 20% worse long-term memory (LTM) (p < 0.01) and lower BDNF concentration in the hippocampus (-14.6%; p < 0.05) when compared to non-insulin-resistant rats (CON). An acute bout of RE restored LTM (-9.7% pre vs. post; p > 0.05) and increased BDNF concentration in the hippocampus (9.1%; p < 0.05) of insulin-resistant rats compared to REST. Thus, an acute bout of RE can attenuate the adverse effects of IR on memory and neurotrophic factors in rats, representing a therapeutic tool to alleviate the IR impact on the brain.

Immunological Aspects of Depressive Disorder - The Review

Abstract Depression represents a mood disorder and is considered to be one of the most common mental disorders in general. World Health Organization estimates that depression will be the leading cause of disability-adjusted life years, until 2030. Depression is a complex heterogeneous disorder where immune system and its regulation play an important role. Innate and adaptive immunity mechanisms are included, along with processes of immune activation and suppression. The expression of humoral factors of innate immunity, especially pro-inflammatory cytokines, is increased, whereas the intensity of cellular immune mechanisms, primarily T cells and NK cells, are impaired. The influence of pro- inflammatory cytokines on depression is reflected in their effect on certain enzymes and ensuing reduction of neurotransmitters serotonin and dopamine. They also affect the neuroendocrine function in central nervous system, resulting in increase of cortisol levels and inactivation of glucocorticoid receptors in the periphery, which leads to neurodegeneration and decrease in neurotransmitter production. Certain cytokines affect neuroplasticity through the decreasing of concentration of neurotrophic brain factor and induction of brain cell apoptosis. The results are often contradictory talking about mechanisms of adaptive immunity. On one hand, an increased activity of Tlymphocytes is observed, while on the other, there are evidence of spontaneous apoptosis and impaired function of these cellsin depression. In addition, neuroprotective role of autoreactive and regulatory T cells in prevention of depression has also been demonstrated. The aim of this paper is to analyze the current knowledge on the role of immune mechanisms in the pathogenesis of depression.

Methanol leaf extract of Leptadenia hastata ameliorates chronic, unpredictable, mild stress-induced depression

Leptadenia hastata (Pers) Decne is a tropical herb widely used in the phytotherapy of neuropsychiatric disorders, including depression. Despite the availability of synthetic antidepressant drugs, depression remains a major medical problem. The study aimed to evaluate the effect of methanol leaf extract of Leptadenia hastata (LHME) on chronic unpredictable mild stress-induced depression. Acute toxicity of Leptadenia hastata was determined using Organization for Economic Co-operation and Development (OECD) guidelines. The chronic unpredictable mild stress (CUMS) model-induced depression involves the evaluation of baseline behavioural changes in the sucrose preference test, open field test, and tail suspension test. The brain-derived neurotrophic factor (BDNF) concentrations and serum cortisol were assessed using an enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were also assessed using standard procedure. The median lethal dose (LD50) value was &gt; 5000 mg/kg. LHME at doses of 250 – 1000 mg significantly (p&lt;0.01) decreased CUMS-induced depression in a dose-dependent manner. LHME significantly (p&lt;0.01) reversed depression associated weight loss from 14.00±0.62 g in week two to 22.57±1.13 g in week five of the experiment. It also increased sucrose consumption in the sucrose preference test (SPT) from 4.29±0.52 ml in week two to 9.71±0.68 ml in week five. The LHME also significantly (p&lt;0.01) decreased the duration of immobility from 190.00±4.55 sec in week two to 158.00±3.83 sec in week five in the tail suspension test (TST). Furthermore, LHME at the tested dose significantly (p&lt;0.01) increased the locomotor activity from 36.29±1.25 sec in week two to 62.43±1.73 sec in week five in the open field test (OFT). LHME significantly (p&lt;0.01) and dose-dependently increased the levels of BDNF (204.74±22.97 pg/ml) and decreased the levels of plasma cortisol (0.98±0.06 ng/ml). However, treatment with LHME and the standard drug imipramine did not significantly change SOD activity and the MDA level in CUMS-induced mice. The findings demonstrated that LHME ameliorates CUMS-induced depressive-like behaviours, and its effect is possibly mediated via the neuroendocrine (cortisol) and neurotrophic (BDNF).

Serum brain-derived neurotrophic factor concentration is different between autism spectrum disorders and intellectual disability children and adolescents

PurposeRecent studies showed that mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF are associated with autism spectrum disorders (ASD). Whether their levels are different between ASD and intellectual disability (ID) subjects is not clear. The aim of this study is to compare the serum mBDNF and proBDNF concentration, and mBNDF/proBDNF ratio in ASD and ID volunteers. MethodsChildren and adolescents with ASD or ID between the ages of 4 and 22 were recruited in Tianjin, China. Serum mBDNF and proBDNF level were tested and Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Wechsler Intelligence Scale for Children (WISC), and Childhood Autism Rating Scale (CARS) evaluations were conducted. ResultsSerum mBDNF concentration and the ratio of mBDNF to proBDNF was higher in ASD subjects than that in ID subjects (P = 0.035 and P < 0.001, respectively), while serum proBDNF of ASD participants was lower compared to that of ID participants (P < 0.001). CARS score was positively correlated with serum mBDNF level (r = 0.33, P = 0.004) and m/p ratio (r = 0.39, P < 0.001), and negatively correlated with serum proBDNF level (r = −0.39, <0.001) after adjusting for age and IQ. The AUC of mBDNF, proBDNF, and m/p ratio were 0.741, 0.790, and 0.854, respectively, after adjusted for age and IQ. ConclusionSerum mBDNF, proBDNF and m/p ratio were different between ASD and ID group. The three biomarkers displayed good diagnostic values for classification of ASD and ID subjects.

Effects of polyunsaturated fatty acids on interleukin-6 and brain-derived neurotrophic factor in monosodium glutamate-induced depression male rats

Background: Depression is the most common psychiatric disorder affecting around 5% of the population worldwide. It leads to morbidity and affects quality of life. Monosodium glutamate (MSG) popularly called a tastemaker is used as a food additive in fast food and other processed foods. MSG has been implicated in causing depression. Since many adolescents and children are being habituated to fast foods, the current study is to evaluate the effects of polyunsaturated fatty acids (PUFAs) supplementation on plasma concentration of brain-derived neurotrophic factor (BDNF) and IL-6 which are important biochemical and immunological markers found in depression. Aims and Objectives: The aim of the current study was to assess the effect of supplementation of PUFA on MSG-induced depression in Wistar albino rats. Materials and Methods: The present prospective interventional study was conducted on 3-month-old, 24 male Wistar albino rats (weighing 200–300 g) for 21 days. The study group was divided into four equal groups among which 1st group that is control received distilled water with carboxymethylcellulose (CMC), the 2nd group positive control group received 500 mg of MSG along with CMC, the 3rd group normal control with PUFA received PUFA dissolved in CMC and the 4th group was positive control with PUFA received MSG dissolved in CMC and PUFA intervention was introduced from the 7th day. The study period was for 21 days and the 22nd day was an acclimatization day. The parameters in the blood samples of the rats were tested on the 23rd day using an ELISA kit and results were analyzed using Tukey’s post hoc test among the various groups and it was taken as statistically significant when the P &lt; 0.05. Results: Among the groups, IL-6 levels raised and BDNF levels dropped in plasma of MSG-induced depressed rats. In PUFA-treated MSG-induced depressed rats, the plasma level of IL-6 was reduced and there was a significant rise in BDNF levels. Conclusion: PUFA supplementation is effective in treating MSG-induced depression in rats.

Influence of rehabilitation with the use of sulphide and hydrogen sulphide baths on the concentration of the brain-derived neurotrophic factor (BDNF) and selected parameters of cognitive, executive and affect functions in multiple sclerosis patients

Aim: To compare the blood serum BDNF concentration in MS patients before and after a standard three-week rehabilitation offered by the NHF. The study compared the expected growth of the BDNF concentration in a group of patients rehabilitated with the help of standard kinesiotherapy and a group of patients rehabilitated with kinesiotherapy plus sulphide and hydro sulphide baths as well as the results of the assessment of the cognitive and executive functions of MS patients in the two groups. Materials and methods: Participants in the study were divided into 3 groups of 20 people each. Group 1. MS patients rehabilitated for 3 weeks in the Day Ward of the Rehabilitation Clinic – standard kinesiotherapy. Group 2. MS patients rehabilitated for 3 weeks in the Day Ward of the Rehabilitation Clinic – kinesiotherapy with sulphide baths. Group 3. Healthy volunteers – occasional BDNF determination. In the group of MS patients the BDNF concentration was determined prior to and after the rehabilitation. Group 3 was monitored for BDNF levels initially lower than in MS patients. Results: Rehabilitation of MS patients with kinesiotherapy and sulphide baths causes a statistically higher growth of BDNF concentration than rehabilitation alone in this group of patients (p&lt;0.001). Results of neuropsychological tests of MS patients rehabilitated with kinesiotherapy and balneotherapy elements are statistically better than of patients rehabilitated with kinesiotherapy (p&lt;0.033). Conclusions: Research findings show that sulphide and hydro sulphuric baths seem to be a valuable supplement to MS patients’ rehabilitation.

ADSC-Exos outperform BMSC-Exos in alleviating hydrostatic pressure-induced injury to retinal ganglion cells by upregulating nerve growth factors.

Mesenchymal stem cells (MSCs) have protective effects on the cornea, lacrimal gland, retina, and photoreceptor cell damage, which may be mediated by exosomes (exos) released by MSCs. To investigate the ameliorating effect of exos derived from different MSCs on retinal ganglion cell (RGC) injury induced by hydrostatic pressure. The RGC injury model was constructed by RGC damage under different hydrostatic pressures (40, 80, 120 mmHg). Then RGCs were cultured with adipose-derived stem cell (ADSC)-Exos and bone marrow-derived stem cell (BMSC)-Exos. Cell Counting Kit-8, transmission electron microscopy, flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction, and western blotting were performed to detect the ameliorating effect of exos on pressure-induced RGC injury. ADSC-Exos and BMSC-Exos were successfully isolated and obtained. The gibbosity of RGCs was lower, the cells were irregularly ellipsoidal under pressure, and the addition of ADSC-Exos and BMSC-Exos significantly restored RGC morphology. Furthermore, the proliferative activity of RGCs was increased and the apoptosis of RGCs was inhibited. Moreover, the levels of lactate dehydrogenase and apoptosis-related proteins were increased, and the concentrations of antiapoptotic proteins and neurotrophic factors were decreased in damaged RGCs. However, the above indicators were significantly improved after ADSC-Exos and BMSC-Exos treatment. These findings indicated that ADSC-Exos and BMSC-Exos could ameliorate RGC injury caused by hydrostatic pressure by inhibiting apoptosis and increasing the secretion of neurotrophic factors.

Association between plasma brain-derived neurotrophic factor level and Alzheimer's disease: a Mendelian randomization study.

High brain-derived neurotrophic factor (BDNF) concentrations have been found to be associated with a decreased risk of Alzheimer's disease (AD) in observational studies, but the causality for this association remains unclear. Therefore, we aimed to examine the association between genetically determined plasma BDNF levels and AD using a two-sample Mendelian randomization (MR) method. Twenty single-nucleotide polymorphisms associated with plasma BDNF concentrations were identified as genetic instruments based on a genome-wide association study with 3301 European individuals. Summary-level data on AD were obtained from the International Genomics of Alzheimer's Project, involving 21,982 AD cases and 41,944 controls of European ancestry. To evaluate the relationship between plasma BDNF concentrations and AD, we employed the inverse-variance weighted method along with a series of sensitivity analyses. The inverse-variance weighted MR analysis showed that genetically determined BDNF concentrations were associated with a decreased risk of AD (odds ratio per SD increase, 0.91; 95% confidence interval, 0.86-0.96; p =0.001). The association between plasma BDNF concentrations and AD was further confirmed through sensitivity analyses using different MR methods, and MR-Egger regression suggested no directional pleiotropy for this association. Genetically determined BDNF levels were associated with a decreased risk of AD, suggesting that BDNF was implicated in the development of AD and might be a promising target for the prevention of AD.

Attenuating DNA hypermethylation enhances insulin signaling and reduces apoptosis in an in vitro model of DLB

AbstractBackgroundDementia with Lewy bodies (DLB) is the second most prevalent degenerative dementia after Alzheimer’s disease (AD). The cause of DLB is known to be associated with abnormal protein aggregations called Lewy bodies within affected neurons. Studies have shown that Lewy bodies are mainly composed of α‐synuclein. Normal α‐synuclein is a water‐soluble monomer. However, when triggered by certain factors, the folding of the protein changes, causing it to aggregate and accumulate inside neurons. Previously, we have demonstrated that amyloid β (Aβ) can promote α‐synuclein aggregation and neurotoxicity, which provides a molecular mechanism that reasonably explained the pathogenesis of DLB. A major risk factor for DLB is known to be aging, but its role in disease progression, especially with regard to epigenetic regulation, is still unclear.MethodIn this study, we investigated whether DNA hypermethylation, a common phenomenon in cellular aging, might be a factor in the progression of DLB. Through the in vitro experimental mode of DLB, we analyzed the content of α‐synuclein aggregations, the difference in cell viability and the activity changes of methylation‐related pathways in mouse HT‐22 neuronal cells.ResultWe found that the DLB neuronal cells display a significant tendency to undergo DNA hypermethylation, which inhibits stemness and reduces the content of neurotrophic factors. This makes it more difficult for neuronal cells to survive under stress. In addition, DLB neuronal cells also showed significant insulin resistance, which interferes with autophagic clearance, upregulates the senescence‐related pathways, and exacerbates the aggregation and accumulation of α‐synuclein.ConclusionDLB cells significantly increase the hypermethylation and thus inhibit insulin signaling, making the affected cells more vulnerable to neurotoxicity. Accordingly, the administration of epigenetic regulators by targeting neuronal DNA hypermethylation may lead to develop novel therapeutic strategies against DLB.

An Exosome-Rich Conditioned Medium from Human Amniotic Membrane Stem Cells Facilitates Wound Healing via Increased Reepithelization, Collagen Synthesis, and Angiogenesis.

Tissue regeneration is an essential requirement for wound healing and recovery of organs' function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 × 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.

Efficient degradation of imidacloprid by surface discharge cold plasma: Mechanism of interaction between ROS and molecular structure and evaluation of residual toxicity

Incorrect use of neonicotinoid pesticides poses a serious threat to human and pollinator health, as these substances are commonly present in bee products and even drinking water. To combat this threat, the study developed a new method of degrading the pesticide imidacloprid using surface discharge cold plasma oxidation technology. The study showed that this method achieved a very high efficiency of imidacloprid degradation of 91.4%. The main reactive oxygen species (H2O2, O3, ·OH, O2-, 1O2) effectively participated in the decomposition reaction of imidacloprid. Reactive oxygen species were more sensitive to the structure of the nitroimine group. Density functional theory (DFT) further explored the sites of reactive oxygen species attack on imidacloprid and revealed the process of energy change of attacking imidacloprid. In addition, a degradation pathway for imidacloprid was proposed, mainly involving reactive oxygen species chemisorption, a ring-opening intermediate, and complete cleavage of the nitroimine group structure. Model predictions indicated that acute oral and developmental toxicity were significantly reduced after cold plasma treatment, as confirmed by insect experiments. Animal experiments have shown that plasma treatment reduces imidacloprid damage to mice hippocampal tissue structure and inhibits the reduction of brain-derived neurotrophic factor content, thus revealing the detoxification mechanism of the body.

Brain-Derived Neurotrophic Factor (BDNF) Concentration Levels in Cerebrospinal Fluid and Plasma in Patients With Glioblastoma: A Prospective, Observational, Controlled Study.

Objective Glioblastomas (GBMs) are among the most frequent and most malignant of untreatable brain tumors. A GBM marker could accelerate diagnosis and facilitate therapeutic monitoring. This prospective, observational, controlled study compared brain-derived neurotrophic factor (BDNF) levels in cerebrospinal fluid (CSF) and plasma between patients with GBM and a control group. Materials and methods Patients in the observational group underwent elective GBM resection (n=24, 55.8%).Control patients (n=19, 44.2%) had elective brain surgery for an unrelated, non-neoplastic, non-traumatic pathology. We measured BDNF levels in tumors, CSF, and plasma with enzyme-linked immunosorbent assay (ELISA). Peripheral blood and CSF samples were collected before surgery, and tumors were sampled intraoperatively. We analyzed correlations between BDNF levels and patient sex, age, seizures, smoking, diabetes mellitus (DM), and the use of selected antiepileptic drug (AED) and antihypertensive drug groups. Results The mean CSF BDNF concentration was significantly lower in patients with GBM (6.5 pg/mL) than in controls (11.48 pg/mL) (p=0.002). Similarly, the mean plasma BDNF concentration was significantly lower in patients with GBM (288.59 pg/mL) than in controls (574.06 pg/mL) (p=0.0005). None of the examined factors influenced CSF, plasma, or tumor tissue BDNF concentrations (p>0.05). Conclusion Plasma and CSF BDNF levels were significantly lowerin adults with GBM than in controls. Thus, CSF and plasma BDNF levels may aid in GBM diagnoses. Further prospective studies are required.

Исследование роли нейротрофических факторов в регуляции регенерационных процессов в поврежденных соматических нервах при действии пептидного препарата «Семакс»

The content of neurotrophic factors in damaged somatic nerves under the action of the drug «Semax» was studied and their role in the regulation of regenerative processes in injured nerve conductors was established. It has been shown that intramuscular administration of the drug is accompanied by a significant increase in the level of NGF and NT-3 both in the proximal and distal parts of the nerve. At the same time, there are no significant changes in the quantitative content of neuroregulin-1 against the background of its use. The data obtained suggest that one of the mechanisms of action of Semax is its ability to interact with Schwann cells and stimulate the release of NGF and NT-3, which facilitate the regeneration of damaged axons and do not affect the synthesis of neuroregulin-1. In addition, the study of the quantitative content of individual protein fractions showed that the drug «Semax» has the most pronounced effect on the level of neurofilament-H in both segments of the nerve conductor, which indicates the important role and activation of the mitogen-activated protein kinase (MAPK / ERK) signalling pathway, which regulates processes of cytoskeletal protein synthesis and axon growth. Nevertheless, it was shown that in the variant of the experiment using Semax, there was a decrease in the level of GAP-43, which is a key marker of axonal growth, both in the proximal and distal segments of the nerve. The data obtained most likely indicate that the intramuscular administration of the drug does not affect the processes of axon growth, but is aimed at maintaining the survival of neurons and accelerated restoration of the functional state of nerve fibres, which is also confirmed by the appearance of an action potential and the ability of the nerve to conduct it against the background of the use of the Semax drug.

Exploring the Relationship between Mood Disorders and Coexisting Health Conditions: The Focus on Nutraceuticals.

Major depressive disorder and bipolar disorder are the leading causes of global disability. Approximately 50% of patients fail to attain remission, prompting a pronounced focus on the significance of dietary patterns and specific nutrients within the pathophysiology of mood disorders. The connection between chronic diseases and mood disorders follows a bidirectional pattern: physical ailments are interrelated with affective disorders, and, concurrently, mood symptoms often precede chronic diseases and have the potential to worsen their prognosis. Nutraceuticals affect factors that could potentially impact the onset of mood disorders: monoamines and brain-derived neurotrophic factor (BDNF) concentrations, neuroinflammation, oxidative stress, and sleep quality. Furthermore, mood disorders rarely manifest in isolation. Typically, such patients concurrently experience other mental disorders or somatic comorbidities: obesity, hypertension, diabetes, polycystic ovary syndrome (PCOS), etc., where providing nutritional support is also pertinent. To optimize the therapeutic approach for individuals with mood disorders, incorporating nutritional support may not solely ameliorate symptoms stemming directly from the mental condition, but also indirectly through interventions targeting comorbidities.