Brain-derived Neurotrophic Factor Research Articles

New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD).

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that may develop after experiencing traumatic events. Preclinical studies use various methods to induce PTSD-like models such as fear-conditioning, single-prolonged stress (SPS), restraint stress, and social defeat. Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophin in mood regulation. Evidence shows BDNF changes in different neuropsychiatric disorders particularly PTSD. This review examined BDNF alterations in preclinical rodent models of PTSD where we demonstrated a wide range of paradoxical changes in BDNF. We found that the fear-conditioning model produced the most inconsistent alterations in BDNF, and suggest that conclusions drawn from these changes be approached with caution. We suggest that BDNF maladaptive changes in social defeat and restraint stress models may be related to the duration of stress, while the SPS model appears to have more consistent results. Ultimately, we propose that evaluating BDNF alterations in the process of treating PTSD symptoms may not be a reliable factor.

Reduced Serum Brain-Derived Neurotrophic Factor in Infants Affected by Severe Bronchiolitis.

Bronchiolitis is an acute viral infection of the lower respiratory tract, typical of infants in their first year of life and causing hypoxia in the most serious cases. Bronchiolitis recognizes various demographic risk factors that are associated with greater clinical severity; however, no laboratory factors are yet able to correlate with the clinical severity. Neurotrophins as Brain-Derived Neurotrophic Factor (BDNF) are mediators of neuronal plasticity. BDNF is constitutively expressed in smooth muscle cells and epithelium of the lower respiratory tract, and as it is released during inflammatory conditions, serum levels may have a relevant role in the prognosis of infants with bronchiolitis. In the present pilot study, we aimed to disclose the presence of serum BDNF in infants hospitalized with bronchiolitis at discharge as a disease severity indicator. Serum BDNF, measured at hospital discharge, was significantly lower in severe bronchiolitis (expressed as O2-supplemented infants). Furthermore, no changes were disclosed for the Tropomyosin receptor kinase B, the main BDNF receptor and neurofilament light chain, a biomarker of neuronal degeneration. Low serum BDNF in infants with severe bronchiolitis could be associated with a higher utilization by lung cells or with an altered production by lung cells. Therefore, further research is required to study if a decreased production or increased consumption of this biomarker is at the base of the above-mentioned findings.

Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling

AimsThis study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling. Materials and methodsFive groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days. Key findingsResults showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP. SignificanceThese findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.

Correlation of physical activity with cognition and mental health in medical students

Low physical activity increases the number of non-communicable diseases. This phenomenon occurs in medical students. This study aimed to determine the correlation between sedentary behavior and physical activity on cognition, mental health, cortisol, and brain derived neurotropic factor (BDNF). Using a cross-sectional design of observational study, eighty-six medical students were involved in this study. The subjects were interviewed to assess cognitive function and depression levels. Saliva was taken to measure cortisol and BDNF level. Bivariate analysis was performed using the Spearman test. Depression is the only variable that correlates significantly with habitual physical activity (p=0.025, r=-0.214). Sedentary behavior has a weak correlation with cognitive failure, anxiety, and depression ([p=0.046, r=0.216]; [p=0.039, r=0.223]; [p=0.011, r=0.273]). The results found that high physical activity improves mental health and cognition. This study suggested that physical activity can alleviate symptoms of depression and anxiety among medical students.

Uncovering the effects and mechanisms of tea and its components on depression, anxiety, and sleep disorders: A comprehensive review

Depression, anxiety and sleep disorders are prevalent psychiatric conditions worldwide, significantly impacting the physical and mental well-being of individuals. The treatment of these conditions poses various challenges, including limited efficacy and potential side effects. Tea, a globally recognized healthful beverage, contains a variety of active compounds. Studies have shown that consuming tea or ingesting its certain active ingredients have a beneficial impact on the mental health issues mentioned above. While the effects of tea on physical health are well-documented, there remains a gap in our systematic understanding of its impact on mental health. This article offers a thorough overview of animal, clinical, and epidemiological studies examining tea and its components in the treatment of depression, anxiety, and sleep disorders, and summarizes the associated molecular mechanisms. The active ingredients in tea, including L-theanine, γ-aminobutyric acid (GABA), arginine, catechins, theaflavins, caffeine, theacrine, and several volatile compounds, may help improve depression, anxiety, and sleep disorders. The underlying molecular mechanisms involve the regulation of neurotransmitters, including monoamines, GABA, and brain-derived neurotrophic factor (BDNF), as well as the suppression of oxidative stress and inflammation. Additionally, these ingredients may influence the microbiota-gut-brain (MGB) axis and the hypothalamic–pituitary–adrenal (HPA) axis. This review provides valuable insights into the effects and mechanisms by which tea and its components regulate depression, anxiety, and sleep disorders, laying the groundwork for further research into relevant mechanisms and the development of tea-based mental health products.

Bedtime banana and milk intake on sleep and biochemical parameters.

This study aimed to evaluate the effects of milk and banana given as a bedtime snack to patients with primary insomnia on sleep parameters and some biochemical parameters such as brain-derived neurotrophic factor, leptin, and ghrelin. 21 patients with insomnia who met the inclusion criteria participated in this study. The patients were divided into 3 parallel groups: banana, milk and control. The intervention group were given either 1 portion of banana or just 200 mL of whole-fat milk at bedtime. The control group did not consume any non-routine food. Venous blood samples were taken at baseline and after the study from patients to measure brain-derived neurotrophic factor, leptin and ghrelin concentrations. Sleep quality and architecture were determined by polysomnography and Pittsburg Sleep Quality Index. Pittsburg Sleep Quality Index scores of the banana and milk group were found to be lower after intervention (p<0.05). In terms of polysomnography, the total sleep time of the milk group was found to be significantly higher than baseline. Serum ghrelin concentration of the milk group decreased significantly compared to baseline. Bedtime milk or banana intake was effective in dealing with insomnia. Foods rich in tryptophan, such as banana and milk, given at bedtime, may improve sleep parameters and appetite hormones.

Interplay of serum BDNF levels and childhood adversity in predicting earlier-onset post-traumatic stress disorder: A two-year longitudinal study

This longitudinal study explored the intricate relationships between serum Brain-Derived Neurotrophic Factor (sBDNF) levels, exposure to childhood adversities, and the subsequent development of Post-Traumatic Stress Disorder (PTSD), distinguishing between earlier- and delayed-onset forms over a two-year follow-up period in individuals sustaining physical injuries. We recruited patients presenting with moderate to severe physical injuries at a trauma center, conducting baseline assessments of sBDNF levels and childhood adversities through the Adverse Childhood Experiences (ACE) questionnaire. Additionally, detailed socio-demographic and clinical data were compiled. The Clinician-Administered PTSD Scale for DSM-5 was employed to diagnose PTSD at 3, 6, 12, and 24 months post-injury. Binary and multinomial logistic regression analyses were applied to elucidate the interactions between sBDNF levels, childhood adversities, and PTSD onset patterns. Among 895 participants, PTSD was diagnosed in 107 individuals (11.9 %), with 76 (8.4 %) exhibiting symptoms indicative of earlier-onset PTSD and 31 (3.5 %) demonstrating delayed-onset PTSD. Significantly, lower sBDNF levels were associated with a higher risk of earlier-onset PTSD specifically in the context of childhood adversities. This association was not observed in individuals without childhood adversities or in those with delayed-onset PTSD. The findings suggest a complex and critical interplay between neurobiological factors, specifically sBDNF levels, and early life adversities in influencing the timing of PTSD onset, potentially deepening the understanding of PTSD etiology.

Transgenerational Impacts of Oxidative Damage Induced by Prenatal Ethanol Exposure on Spatial Learning/Memory and BDNF in the Hippocampus of Male Rats

Alcohol consumption during pregnancy harms fetal development, leading to various physical and behavioral issues. This study investigates how prenatal ethanol exposure triggers oxidative stress (OS) and affects neurotrophic factors (NTFs), particularly brain-derived growth factor (BDNF) gene expression in the hippocampus, influencing learning and memory decline across two generations of male offspring from ethanol-exposed female rats. A rat model of fetal alcohol spectrum disorder (FASD) was initially generated to reflect on the deficits in the first generation, and then those transmitted via the male germline to the unexposed male ones. The pregnant rats were thus divided into four groups, namely, the control group (CTRL) receiving only distilled water (DW), and three groups being exposed to ethanol (20 %, 4.5 g/kg) by oral gavage, during the first 10-day gestation (FG), the second 10-day gestation (SG), and the entire gestation (EG) periods. Subsequent Morris water maze (MWM) tests on male offspring revealed spatial learning deficits during the second and entire gestational periods in both generations. Analysis of antioxidant enzyme activity including glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA), and BDNF gene expression in the hippocampus further highlighted the impacts of prenatal ethanol exposure. The study results demonstrated that prenatal ethanol exposure caused spatial learning/memory deficits during the SG and EG, altered antioxidant enzyme activity, and reduced BDNF gene expression in both generations. The findings underscore the role of OS in developmental and behavioral issues in FASD rat models and suggest that lasting transgenerational effects in the second generation may stem from alcohol-induced changes.

Stress-resilient effect of Spirulina platensis on zebrafish chronic unpredictable stress model

Spirulina platensis is rich in nutritional profile and a great source of prebiotic with neuro-protective properties. Stress is an inevitable part of today's lives, affecting people differently, and individuals with resilient adaptations are less vulnerable to it. The present study aims at evaluating Spirulina as a prebiotic supplement in the early life of zebrafish to cope with chronic unpredictable stress (CUS) in its later stage of life. Zebrafish 5dpf larvae were fed with 1% Spirulina formulated diet for 90 days, and then adult zebrafish were subjected to CUS for 15 days to evaluate the diet's response to chronic stress. The observations were compared by studying the anxiety level through behavioural test, gut microbiota composition analysis, and the effect on the myelin sheath at the ultrastructural and molecular levels. In zebrafish given the Spirulina supplemented diet, CUS did not induce anxiety-like behaviour, Spirulina supplementation lowered the Firmicutes to Bacteroidetes ratio and helped in myelin protection, with a significant decrease in the myelin g-ratio and upregulation of myelin-related genes bdnf, mpz, olig2 and sox10 which resulted in mitigating the effect of stress as compared to fish fed with a normal diet. To conclude, Spirulina supplementation in the early life of zebrafish helps to reduce the effects of a chronic unpredictable stress. However, Spirulina's protective effect against overall stress needs to be evaluated further.

Central neurophysiological mechanisms of stress resistance in post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a severe, disabling syndrome that is induced by an extremely powerful negative impact on the people’s psyche. Symptoms of the disease most often do not appear in the entire population of stressed people and not immediately, but after some indefinite period of time. The disease is caused by central, genetic, epigenetic and neurobiological determinants, interactively integrated within the underlying social and natural-anthropogenic context. The simultaneous development of a pathological reaction from the hypothalamic-pituitary-adrenal, sympathoadrenal and immune systems was established. Information on the state of the main biogenic and amino acid neurotransmitters of the central nervous system in PTSD is presented. Researchers are currently focusing on peptide hormones such as brain-derived neurotrophic factor, neuropeptide Y, and leptin, which can be used to diagnose and treat PTSD. An analysis of the literature led to the conclusion that about the characteristics of stress-resistant people and animals very little is still known.

Penetratin and Mannose-Functionalized Cannabidiol Lipid Nanoparticles Encapsulating the BDNF Gene Reduce Amyloid-Induced Inflammation.

Inflammation is emerging as a critical player in the disease progression of Alzheimer's disease (AD) by its interaction with amyloid beta plaques in a feed-forward loop. There is also a decline in the nourishment and enriching neurotrophic factor, brain-derived neurotrophic factor (BDNF), in the brain. Therefore, supplementing the brain with BDNF by gene delivery and delivering the anti-inflammatory agent, cannabidiol (CBD) in this case, to mitigate inflammation-induced disease cascade offers an attractive treatment strategy. To achieve the brain localization of CBD and pBDNF, lipid nanoparticles (LNPs) functionalized with mannose and penetratin were utilized. CBD and pBDNF were successfully encapsulated in the LNPs (more than 80%) with a size less than 180 nm, polydispersity index less than 0.25, and zeta potential of 23 mV. CBD was released from the formulation over a period of a week. The dual-functionalized LNPs demonstrated higher cellular uptake of CBD and expressed a significantly higher amount of BDNF (p-value <0.05) after transfection than their nonmodified counterparts in four brain cell lines, i.e., brain endothelial cells (b.END3), immortalized microglia cells (IMGs), primary astrocytes, and primary neurons. Similarly, the permeation of CBD through the dual-modified LNPs across the in vitro coculture blood-brain barrier model was significantly higher (p-value <0.05) compared to free CBD or nonfunctionalized nanoparticles. The LNPs demonstrated anti-inflammatory activity against lipopolysaccharides and human amyloid beta1-42 oligomer induction as they reduced the protein and mRNA expression of pro-inflammatory cytokines TNF-α (p < 0.05) and IL-1β (p < 0.05) in IMG cells. In summary, the penetratin and mannose-functionalized LNPs encapsulating CBD and pBDNF could serve as a promising therapy in AD, requiring further validation in animal models.

RTMS Modulation of Behavioral and Biological Measures in 3xTg-AD Mice

Background/Objectives: The biological basis for behavioral manifestations of Alzheimer’s disease remains unclear. Emotional and behavioral alterations of Alzheimer’s disease can result in substantial caregiver burden and lack effective management. This study expands upon previous work investigating behavioral alterations in mice with Alzheimer’s disease and a potential treatment of increasing brain-derived neurotrophic factor (BDNF) using repetitive transcranial magnetic stimulation (rTMS). Methods: A total of 47 3xTg-AD (Alzheimer’s) and 53 B6 (wildtype) mice were administered with ANA12 (an antagonist of TrkB receptor) or Vehicle (saline) and then rTMS or Sham treatment daily. After 14 days of treatments and injections, mouse behavior was assessed under various behavioral cognitive tests. Mice were then perfused, and brain samples were processed for histology and protein assays. Brain homogenates were analyzed for BDNF and its downstream signaling molecules. Results: Open field testing demonstrated that 3xTg-AD mice spent more time in the center than B6 mice. 3xTg-AD-Sham mice injected with ANA12 were the only group to travel significantly less distance than B6-ANA12-Sham or B6-Vehicle-Sham mice (p &lt; 0.05), while 3xTg-AD-rTMS mice (irrespective of injection) were not significantly different from B6 mice. 3xTg-AD mice had significantly greater measured levels of BDNF and TrkB than the wild-type mice. Conclusions: Treatment of Alzheimer’s disease using rTMS positively affects elements of hypoactivity, but not all behavioral abnormalities. rTMS shifted 3xTg-AD open field behavioral test measures, generating significant differences between untreated 3xTg-AD and B6 genotypes. Despite its benefit, further investigation of rTMS as a treatment for Alzheimer’s disease as well as its biological underpinnings are needed.

Research progress of mechanism of acupuncture and moxibustion on prevention and treatment of Alzheimer's disease based on the neuronal cell cycle re-entry

Alzheimer's disease (AD) is the most common type of dementia. Studies have shown that neuronal cell cycle re-entry is an abnormal change in the early stage of AD, and it is also one of the key reasons for mediating neuronal death. The mechanism of acupuncture and moxibustion in treating AD may be related to the regulation of abnormal cell cycle. In this article, we reviewed the occurrence of AD neuronal cell cycle re-entry and its mediated cell death mechanism, listed the factors affecting neuronal cell cycle re-entry, explored the possible mechanism of acupuncture and moxibustion in preventing and treating AD by regulating AD cell cycle protein, AD neuronal cell cycle re-entry influencing factors (β-amyloid protein and Tau protein phosphorylation level, oxidative stress, brain-derived neurotrophic factor), the multi-target regulation of neuronal cell cycle re-entry, so as to provide reference for the application and research of acupuncture and moxibustion in preventing and treating AD.

Effect of He's qiangtong method of acupuncture on serological levels in patients with acute ischaemic stroke

To investigate the repair effects of He's qiangtong method of acupuncture (involved bloodletting technique with strong action of unblocking) on the neurovascular unit of the patients with acute ischemic stroke (AIS) in terms of serological indicators so as to provide new ideas for the treatment of AIS. Seventy subjects with AIS were randomly divided into an observation group (35 cases, 1 case dropped out) and a control group (35 cases , 4 cases dropped out). Patients in the control group were treated with conventional regimen. In the observation group, the bloodletting was operated, combined with the conventional treatment. Bloodletting was performed at Baihui (GV20), Sishencong (EX-HN1) and bilateral Erjian (EX-HN6), using He's qiangtong method of acupuncture, 3 times a week and for 2 weeks. Before and after treatment, the scores of the national institute of health stroke scale (NIHSS), the modified Rankin scale (MRS), and the Barthel index were evaluated；and the serological levels of the serum brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and blood-brain barrier permeability-associated protein (S100β protein) were detected in the two groups. After treatment, NIHSS score and MRS score were decreased (P<0.01), and Barthel score was increased (P<0.01) in both groups. NIHSS score of the observation group was lower than that of the control group (P<0.01). Compared with those before treatment, the content of BDNF in both groups increased (P<0.05), and VEGF content was elevated in the observation group (P<0.05) after treatment. The total effective rate was 100% (34/34) in the observation group, higher than that (67.74%, 21/31) in the control group (P<0.01). He's qiangtong method of acupuncture can promote the recovery of neurological deficits in AIS patients and effectively improve their motor function and the activity of daily living, which may be related to the reconstruction of neurovascular unit in the brain of AIS patients by increasing the levels of serological repair factors.

Combining Network Pharmacology and Transcriptomic Strategies to Explore the Pharmacological Mechanism of Total Ginsenoside Ginseng Root and Its Impact on Antidepressant Effects

Depression is one of the most common neurological diseases, which imposes a substantial social and economic burden on modern society. The purpose of this study was to explore the mechanism of total ginsenoside ginseng root (TGGR) in the treatment of depression through a comprehensive strategy combining network pharmacology, transcriptomics, and in vivo experimental validation. The Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and literature were used to collect the main components and targets of TGGR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to explore the underlying mechanisms. In addition, the chronic unpredictable mild stress (CUMS)-induced C57BL/6 mouse model was used to evaluate the antidepressant activity of TGGR. The results showed that TGGR improved depression-like behavior in mice and increased the decrease in serum 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) levels caused by CUMS. Combined network pharmacology and transcriptomic analysis showed that the AMP-activated kinase (AMPK) signaling pathway mainly enriched the core target. Immunohistochemistry, Western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to confirm whether TGGR exerts antidepressant effects by regulating this pathway. The results showed that TGGR has a regulatory impact on related proteins in the AMPK pathway, and the regulatory effect of TGGR on proteins was inhibited after the administration of related pathway inhibitors. In summary, total ginsenosides may regulate the AMPK signaling pathway and activate the sirtuin 1 (SIRT1) peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) pathway to have therapeutic effects on depression.

Correlation investigation between BDNF (Val66Met/rs6265) polymorphism and attention deficit hyperactivity disorder susceptibility in Chinese mainland population: a meta-analysis

ABSTRACT This meta-analysis evaluated the association between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and the susceptibility to attention deficit hyperactivity disorder (ADHD) in the Chinese mainland population. Eligible documents were selected from online databases including PubMed, Embase, Cochrane Library, CNKI, Wanfang and CBM (updated to 15 October 2023). The evaluation of study quality was conducted according to guidelines of Newcastle-Ottawa Scale. Basic features of patients, OR and 95% CI were retrieved to assess the correlation between ADHD susceptibility and Val66Met polymorphism in four genetic models: allele genetic model (mutation (A) vs. wild-type (G)), additive genetic model (AA vs. GG and AG vs. GG), recessive genetic model (AA vs. AG+GG) and dominant genetic model (AA+AG vs. GG). This study included totally four studies for subsequent meta-analysis. The results indicated that the correlation between ADHD susceptibility and Val66Met polymorphism in A vs. G (OR = 0.8840, 95%CI: [0.6696–1.1672], p = 0.3846), AA vs. GG (OR = 0.8436, 95%CI: [0.5432–1.3102], p = 0.4490), AA+AG vs. GG (OR = 0.8602, 95%CI: [0.6497–1.1391], p = 0.2933), AG vs. GG (OR = 0.9132, 95%CI: [0.7810–1.0679], p = 0.2556) and AA vs. GG+AG (OR = 1.0315, 95%CI: [0.8789–1.2105], p = 0.7044) was not significant. Egger’s test and sensitivity analysis demonstrating the reliability and stability our conclusions, respectively. BDNF Val66Met polymorphism did not contribute to the susceptibility of ADHD in Chinese mainland population.

Leptin/Melanocortin Pathway in Cholelithiasis Patients: A Diagnostic Perspective?

Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. The regulation of biological processes, including energy homeostasis, and control of body weight are key mechanisms that the leptin and melanocortin pathways play a role in. Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. There are various risk factors for the development of gallstone disease, especially weight gain, and obesity is just one of them. This risk factor can be minimized by maintaining appetite and energy balance. Here, leptin and melanocortin pathways are the key mechanisms in maintaining appetite and energy homeostasis. The aim of this study was to investigate the relationship between the levels of LEP, LEPR, TrkB, BDNF, POMC, and MC4R proteins in patients with Cholelithiasis. This study aims to determine the relationship between LEP, LEPR, TrkB, BDNF, POMC, and MC4P protein levels, which play a role in maintaining appetite and energy homeostasis, and cholelithiasis. This study examined 44 patients diagnosed with Cholelithiasis and 44 healthy control subjects who had not previously been diagnosed with any form of Cholelithiasis. The levels of leptin (LEP), Leptin Binds To Leptin Receptors (LEPR), Tropomyosin Receptor Kinase B (TrkB), Brain-Derived Neurotrophic Factor (BDNF), Pro-OpioMelanoCortin (POMC), and Melanocortin- 4 Receptors (MC4R) molecules were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The results were analyzed using the SPSS Software (Version 22.0) program and GraphPad Prism 8.0.1 software. The study found a statistically significant decrease (p < 0.05) in MC4R, TrkB, BDNF, and POMC protein levels in Cholelithiasis patients compared to the control group. There was no statistically significant difference in LEP and LEPR concentration values between the two groups (p=0.247, p=0.674). The proteins MC4R, TrkB, BDNF, and POMC, which are involved in the leptin and melanocortin pathways may play a significant role in Cholelithiasis disease. However, more detailed research on the relevant proteins is needed. Nevertheless, this research will guide new studies.

The mechanism and treatment of cognitive dysfunction in diabetes: A review.

Diabetes mellitus (DM) is one of the fastest growing diseases in terms of incidence worldwide and seriously affects cognitive function. The incidence rate of cognitive dysfunction is up to 13% in diabetes patients aged 65-74 and reaches 24% in those aged >75 years. The mechanisms and treatments of cognitive dysfunction associated with diabetes mellitus are complicated and varied. According to previous studies, hyperglycaemia mainly contributes to cognitive dysfunction through mechanisms involving inflammation, autophagy, the microbial-gut-brain axis, brain-derived neurotrophic factors and insulin resistance. Antidiabetic drugs such as metformin, liraglutide and empagliflozin and other drugs such as fingolimod and melatonin can alleviate cognitive dysfunction caused by diabetes. Self-management, indirect fasting and repetitive transverse magnetic stimulation can also ameliorate cognitive impairment. In this review, we discuss the mechanisms linking diabetes mellitus with cognitive dysfunction and propose a potential treatment for cognitive dysfunction related to diabetes mellitus.

Effect of systemic ozone therapy added to pharmacological treatment on brain-derived neurotrophic factor (BDNF) and cognitive status in post-COVID patients

BACKGROUND: Treatment is required for post-COVID cognitive impairment associated with functional limitations, reduced work capacity, and significant deterioration in quality of life. Pharmacological treatment is ineffective. In this context, physical therapy, especially systemic ozone therapy with potential neuroprotective effects, appears promising. AIM: The aim of the study was to evaluate the effect of systemic ozone therapy added to pharmacological treatment on plasma brain-derived neurotrophic factor (BDNF) levels and cognitive status in patients with post-COVID cognitive impairment. MATERIALS AND METHODS: A total of 140 patients aged 18-45 years with post-COVID asthenic syndrome were evaluated and treated. They were randomized into two groups: an experimental group with 70 subjects who received systemic ozone therapy in addition to pharmacological treatment and the comparator group with 70 subjects who received pharmacological treatment only. Pre- and post-treatment outcomes were assessed using plasma BDNF levels and the Montreal Cognitive Assessment (MoCa) score. RESULTS: Statistically significant differences in BDNF levels (р=0.034) and MoCa scores (р=0.002) were found between the compared groups at the end of therapy (day 30). In our study, adding systemic ozone therapy to pharmacological treatment in patients with post-COVID cognitive impairment normalized BDNF levels and completely improved clinical manifestations of cognitive impairment in 95% of subjects. CONCLUSION: Therefore, systemic ozone therapy can be considered as one of the effective and pathogenetically proven strategies for comprehensive treatment of patients with post-COVID cognitive impairment in the outpatient setting.

Val66Met Polymorphism of the BDNF Gene and Work Intellectual Complexity: Associations with Speed Characteristics of Cognitive Activity in Aging

The high heterogeneity of cognitive aging is explained by the influence of both genetic and environmental factors. It has been shown that increasing cognitive reserve prevents the development of aging-related cognitive impairment. Education and level of professional activity are considered external factors in the formation of cognitive reserve. BDNF (brain-derived neurotrophic factor) is a neurotrophic factor involved in the processes of plasticity of the mature brain. A polymorphism (Val66Met) of the BDNF gene is associated with differential expression of BDNF, suggesting its potential role in the on cognitive training outcomes. The associations between Val66Met polymorphism and the effectiveness of mental training caused by and work intellectual complexity throughout adult life (in our study, a comparison of scientists - SA and people not associated with professional scientific activities — NSA remain unstudied. The objective of the study was to assess the modulating effect of these factors in relation to aging-related changes in the processes of attention and figurative creativity in models that allow us to consider both the efficiency and speed aspects of activity. The study involved 257 healthy young and 162 elderly Caucasians belonging to the groups of SA and NSA. It has been shown that the Val66Met polymorphism of the BDNF gene is associated with the influence of the level of professional activity on the efficiency of cognitive functions only in elderly subjects. At a higher intensity of intellectual activity (SA), Val/Val, but not Val/Met carriers, showed a reduction in the average reaction time in the Attention network test and an increase in fluency when testing figurative creativity compared to similar indicators of elderly subjects in the NSA group. The results obtained indicate greater plasticity of cognitive functions in carriers of the Val/Val genotype and may be used for prediction and development of methods for differentiated correction of age-related cognitive decline.