Neurotrophic Factor Levels Research Articles

Role of Cardiovascular Risk in Associations of Brain-Derived Neurotrophic Factor with Longitudinal Brain and Cognitive Trajectories in Older Adults

ABSTRACT Background Higher levels of brain-derived neurotrophic factor (BDNF) have been associated with better neurocognitive outcomes. BDNF is present in cardiovascular tissue, and some evidence suggests it may benefit cardiovascular function. The current study assessed whether there is a mediating and/or moderating role of cardiovascular health in the relationship between BDNF and brain and cognitive outcomes. Method We examined longitudinal data from 397 older adults (aged 54–89;164 females, 233 males) enrolled in the Alzheimer’s Disease Neuroimaging Initiative with available plasma BDNF, medical, neuroimaging, and cognitive assessments. We used path analysis and linear regression to estimate the mediating and moderating roles of two measures of cardiovascular health, the Framingham Risk Score (FRS) and pulse pressure, in the relationships between BDNF and longitudinal changes in brain structure (white matter hyperintensity volume, hippocampal volume, and primary visual cortex volume) and cognitive function (executive function, episodic memory, and language). Results There was no significant association of plasma BDNF with FRS or pulse pressure (ps > 0.31), precluding mediation. There were no robust associations between BDNF and longitudinal change in any brain structural or cognitive measures (ps > .12). Higher FRS was significantly associated with greater increases in WMH volume (ps < .01). FRS and pulse pressure were not associated with any other brain structural or cognitive outcomes (ps > .07). Conclusion These results suggest that cardiovascular health may not play an important role in the influence of BDNF on neurocognitive health in older adults.

Jianghua Kucha black tea containing theacrine attenuates depression-like behavior in CUMS mice by regulating gut microbiota-brain neurochemicals and cytokines

Theacrine and theaflavins are known for their potential to mitigate depression and cognitive impairment. Jianghua Kucha black tea (JH) contains both compounds, yet its antidepressant properties are seldom documented. This study evaluated the effects of JH on depression in chronic unpredictable mild stress (CUMS) mice and explored the underlying mechanisms through integrative analyses of gut microbiota and fecal metabolomics. JH was found to significantly alleviate CUMS-induced depression-like behavior by improving body weight, food intake, 1% sucrose preference, immobility time, and numbers of crossings and standings compared to Zhuyeqi black tea (ZYQ), which contains theaflavins. JH notably altered the gut microbiota composition, enriching genera such as Turicibacter, Faecalibaculum, Akkermansia, and Desulfovibrio, while inhibiting genera norank_f__Muribaculaceae and Lactobacillus. Additionally, JH modified the fecal metabolite profile, characterized by increased levels of several secondary bile acids (BAs) and decreased levels of several purine intermediate metabolites. Furthermore, JH upregulated levels of monoamine neurotransmitters (5-HT and DA) and brain-derived neurotrophic factor (BDNF), while downregulating pro-inflammatory cytokines IL-6 and TNF-α in brain tissue. These findings suggested that JH could mitigate CUMS-induced depression-like behavior, potentially by modulating gut microbiota composition and function, as well as brain neurochemicals and cytokines.

Effects of variation in exercise training load on cognitive performances and neurotrophic biomarkers in patients with coronary artery disease.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. Visit 1 included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o2peak). Visit 2 included cognitive functions assessment. Thirty-nine patients completed the study (LP: n = 20, NLP: n = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: P < 0.001), whereas BDNF concentration increased (time-effect: P < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.18, P = 0.04), and ΔIGF-1 and Δshort-term/working memory (R2 = 0.17, P = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.45, P = 0.02), ΔBDNF and Δshort-term/working memory (R2 = 0.62, P = 0.004), ΔIGF-1 and Δshort-term/working memory (R2 = 0.31, P = 0.01), and ΔIGF-1 and Δexecutive function (R2 = 0.22, P = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD.NEW & NOTEWORTHY We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.

Regenerative potentials of bone marrow mesenchymal stem cells derived exosomes or its combination with zinc in recovery of degenerated circumvallate papilla following surgical bilateral transection of glossopharyngeal nerve in rats

BackgroundTaste buds’ innervation is necessary to sustain their cell turnover, differentiated taste buds and nerve fibers in circumvallate papilla (CVP) disappear following glossopharyngeal nerve transection. Normally, taste buds recover to baseline number in about 70 days. Bone marrow stem cell (BM-MSC) derived exosomes or their combination with Zinc chloride are used to assess their potential to speed up the regeneration process of CVP following bilateral deafferentation.MethodsTwenty-eight male Sprague-Dawley rats were randomly divided into four groups; Group I: subjected to sham operation followed by IP injection of saline. The other experimental groups (II, III and IV) were subjected to surgical bilateral transection of glossopharyngeal nerve. Group II received single IP injection of saline. Group III received single IV injection of BM-MSC-derived exosomes (100 µg). Group IV received single IV injection of BM-MSC-derived exosomes and single IP injection of zinc chloride (5 mg/kg). After 28 days, CVP was dissected and prepared for histological and histomorphometric analysis, RT-PCR for cytokeratin 8 gene expression, ELISA to assess protein level of brain-derived neurotrophic factor, redox state analysis of malondialdehyde and glutathione content, followed by statistical analysis.ResultsHistopathologically, group II exhibited great tissue damage with marked reduction in taste buds and signs of degeneration in the remaining ones. Group III was close to control group with marked improvement in taste buds’ number and structure. Group IV showed inferior results when compared to group III, with many immature taste buds and signs of degeneration. Statistical results showed that groups I and III have significantly higher values than groups II and IV regarding taste buds’ number, cytokeratin 8, and reduced glutathione. However, malondialdehyde demonstrated high significant values in group IV compared to groups I and III. Regarding brain-derived neurotrophic factor, group III had significantly higher values than group II.ConclusionBM-MSC-derived exosomes have superior regenerative potentials in acceleration of CVP and nerve healing following bilateral transection of glossopharyngeal nerve in contrary to its combination with zinc chloride.Graphical

Neurons enhance blood–brain barrier function via upregulating claudin-5 and VE-cadherin expression due to glial cell line-derived neurotrophic factor secretion

Blood–brain barrier (BBB) prevents neurotoxins from entering central nervous system. We aimed to establish and characterize an in vitro triple co-culture BBB model consisting of brain endothelial cells hCMEC/D3, astrocytoma U251 cells, and neuroblastoma SH-SY5Y cells. Co-culture of SH-SY5Y and U251 cells markedly enhanced claudin-5 and VE-cadherin expression in hCMEC/D3 cells, accompanied by increased transendothelial electrical resistance and decreased permeability. Conditioned medium (CM) from SH-SY5Y cells (S-CM), U251 cells (U-CM), and co-culture of SH-SY5Y and U251 cells (US-CM) also promoted claudin-5 and VE-cadherin expression. Glial cell line-derived neurotrophic factor (GDNF) levels in S-CM and US-CM were significantly higher than CMs from hCMEC/D3 and U-CM. Both GDNF and US-CM upregulated claudin-5 and VE-cadherin expression, which were attenuated by anti-GDNF antibody and GDNF signaling inhibitors. GDNF increased claudin-5 expression via the PI3K/AKT/FOXO1 and MAPK/ERK pathways. Meanwhile, GDNF promoted VE-cadherin expression by activating PI3K/AKT/ETS1 and MAPK/ERK/ETS1 signaling. The roles of GDNF in BBB integrity were validated using brain-specific Gdnf silencing mice. The developed triple co-culture BBB model was successfully applied to predict BBB permeability. In conclusion, neurons enhance BBB integrity by upregulating claudin-5 and VE-cadherin expression through GDNF secretion and established triple co-culture BBB model may be used to predict drugs’ BBB permeability.

Fluoxetine Ameliorates Cognitive Deficits in High-Fat Diet Mice by Regulating BDNF Expression.

High-fat diet (HFD) induced obesity is associated with depression-related behavioral and neurogenic changes and may lead to cognitive impairment. Fluoxetine (FXT), the most commonly used antidepressant, may alleviate depressive symptoms by increasing neurogenesis, but the potential efficacy of FXT for HFD-induced cognitive deficits is unclear. In this study, we established an obese HFD mouse model by feeding three-week-old male C57BL/6N mice with a chronic HFD for 18 weeks, then assessed adipose tissue morphology by magnetic resonance imaging and histopathology, assessed cognitive function by Morris water maze and novel object recognition tests, and detected DCX+ and BrdU+ expression in the hippocampal dentate gyrus (DG) region by immunofluorescence bioassay. Western blot detected brain-derived neurotrophic factor (BDNF) levels and CREB-BDNF pathway-related genes were assayed by Quantitative RT-PCR. The results of the study showed that HFD contributes to obesity and cognitive deficits, and more importantly, it also reduces BDNF expression and neurogenesis levels in the hippocampus. Subsequently, we found that treatment with FXT (10 mg/kg/day) ameliorated chronic HFD-induced cognitive deficits and increased the expression of Nestin, BrdU+, and DCX+ in the DG, restored BDNF expression in the hippocampus and increased the expression of genes related to CREB, BDNF, NGF, and MAPK1. In conclusion, our data elucidated that FXT ameliorates cognitive deficits and reduces chronic HFD-induced neurogenesis by restoring BDNF expression and CREB-BDNF signaling, this provides a good basis and scientific significance for future research on the clinical treatment of obesity.

Plasma Brain-Derived Neurotrophic Factor (BDNF) Levels and BDNF Promoters’ DNA Methylation in Workers Exposed to Occupational Stress and Suffering from Psychiatric Disorders

Introduction: Decreased plasma BDNF (pBDNF) levels have been proposed as a biomarker in the illness phases of mood disorders. This cross-sectional study aimed to evaluate the pBDNF and BDNF promoters’ DNA methylation levels in workers exposed to occupational stress and suffering from work-related stress disorders. Methods: the pBDNF and BDNF exon I and IV promoters’ methylation levels were measured by specific immunoassays and methylation-sensitive high-resolution melting (MS-HRM) in 62 patients with adjustment disorders (AD), 79 patients with major depressive disorder (MDD) and 44 healthy controls. Occupational stress was evaluated in the patients and controls using the Job Content Questionnaire (JCQ). Results: the pBDNF levels were significantly higher in the MDD (p &lt; 0.001) and AD (p &lt; 0.0001) patients than in the controls. The MDD patients showed significantly lower pBDNF levels than the AD ones (p = 0.01). The BDNF exon I and IV promoters’ methylation levels were significantly higher in the MDD patients than in the AD ones (exon I promoter: p = 0.0001, exon IV promoter: p &lt; 0.0001) and controls (exon I promoter: p = 0.0001, exon IV promoter: p &lt; 0.0001). In the patients, but not in the controls, the BDNF promoters’ methylation levels showed significant negative correlations with occupational stress. Conclusions: BDNF could play a key role in the pathophysiology of stress-related disorders and the peripheral elevation of it observed in patients exposed to occupational stress could suggest a protective mechanism for neurons from stress-mediated damage. The elevation of the pBDNF levels, even in MDD, may characterize a “reactive” subtype of depressive episode, while the significant elevation of the BDNF promoters’ methylation levels in depressed patients could indicate a predisposition to more severe illness under stress. Further research is needed, focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases.

Neurons enhance blood-brain barrier function via upregulating claudin-5 and VE-cadherin expression due to glial cell line-derived neurotrophic factor secretion.

Blood-brain barrier (BBB) prevents neurotoxins from entering central nervous system. We aimed to establish and characterize an in vitro triple co-culture BBB model consisting of brain endothelial cells hCMEC/D3, astrocytoma U251 cells, and neuroblastoma SH-SY5Y cells. Co-culture of SH-SY5Y and U251 cells markedly enhanced claudin-5 and VE-cadherin expression in hCMEC/D3 cells, accompanied by increased transendothelial electrical resistance and decreased permeability. Conditioned medium (CM) from SH-SY5Y cells (S-CM), U251 cells (U-CM), and co-culture of SH-SY5Y and U251 cells (US-CM) also promoted claudin-5 and VE-cadherin expression. Glial cell line-derived neurotrophic factor (GDNF) levels in S-CM and US-CM were significantly higher than CMs from hCMEC/D3 and U-CM. Both GDNF and US-CM upregulated claudin-5 and VE-cadherin expression, which were attenuated by anti-GDNF antibody and GDNF signaling inhibitors. GDNF increased claudin-5 expression via the PI3K/AKT/FOXO1 and MAPK/ERK pathways. Meanwhile, GDNF promoted VE-cadherin expression by activating PI3K/AKT/ETS1 and MAPK/ERK/ETS1 signaling. The roles of GDNF in BBB integrity were validated using brain-specific Gdnf silencing mice. The developed triple co-culture BBB model was successfully applied to predict BBB permeability. In conclusion, neurons enhance BBB integrity by upregulating claudin-5 and VE-cadherin expression through GDNF secretion and established triple co-culture BBB model may be used to predict drugs' BBB permeability.

The participation of monoamines in the realization of vasopressin analgesic effects during electrical stimulation of paws in rats

BACKGROUND: Arginine vasopressin has been implicated in the modulation of stress and pain. The influence of a synthetic analogue of arginine vasopressin, 1-deamino-8-D-arginine-vasopressin, оn pain sensitivity, stress reactivity, levels of monoamines and brain neurotrophic factor in a model of paw electrical stimulation in rats has not been studied. AIM: The aim was to evaluate the effect of a synthetic vasopressin analog, 1-deamino-8-D-arginine-vasopressin, on pain sensitivity and the content of norepinephrine, serotonin, dopamine, brain neurotrophic factor in the parietal cortex and spinal cord in electrocutaneous paw stimulation test in rats. MATERIALS AND METHODS: The study was conducted on male Wistar rats who were injected with 1-deamino-8-D-arginine-vasopressin intranasally once a day for 5 days in small (single 20 ng, course 100 ng) and large doses (single 2 ug, course 10 ug). The content of brain neurotrophic factor in the parietal cortex and spinal cord, and corticosterone in blood serum were determined using enzyme immunoassay. The levels of norepinephrine, serotonin, dopamine and their metabolites in the brain were evaluated using high-performance liquid chromatography. RESULTS: 1-Deamino-8-D-arginine-vasopressin in different doses reduced pain sensitivity in rats, more pronounced when administered in large doses. The peptide in small doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid, a metabolite of serotonin; in the spinal cord, it reduced the content of 5-hydroxyindolacetic acid. 1-Deamino-8-D-arginine-vasopressin in high doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid; in the spinal cord ― reduced the content of serotonin and 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine; increased the levels of norepinephrine and homovanilic acid, a metabolite of dopamine. The peptide had no effect on corticosterone levels in the blood and brain neurotrophic factor levels in the brain in rats. CONCLUSIONS: The analgesic effects of 1-deamino-8-D-arginine-vasopressin were revealed with intranasal administration in different subendocrine doses. Regardless of the administered doses, dopamine and serotonin at the supraspinal level were involved in peptide-induced anesthesia; serotonin at the spinal cord level. More pronounced analgesia with the administration of 1-deamino-8-D-arginine-vasopressin in high doses was due to the additional involvement of dopamine and norepinephrine at the spinal cord level.

Vitamin C improved anxiety and depression like behavior induced by chronic unpredictable mild stress in adolescent rats by influencing on oxidative stress balance, neurotransmitter systems, and inflammatory response

ABSTRACT Objectives: Stress is an adaptive response to different events in daily life that could strain physically, emotionally, or psychologically. Adolescence is an important developmental period due to physical, psychological, and social maturation. The aim of our study is to state whether chronic unpredictable mild stress (CUMS) during adolescence in male rats can cause anxiety and depression in adulthood and whether vitamin C (Vit C) can prevent this problem or not. Methods: For this purpose, we performed behavioral tests, including open field test, elevated plus maze, and forced swimming test. In addition, we investigated the metabolism of serotonin, the level of inflammation, oxidative stress and brain-derived neurotrophic factor (BDNF) in the brain cortex tissue of animals. Results: Results indicated that CUMS exacerbates mood-related behaviors by affecting the brain oxidative stress balance, inflammatory response, and serotonin metabolism. Moreover, we found that CUMS-Vit C co-treatment could significantly reverse CUMS-induced complications by restoration of the mentioned biochemical parameters. Discussion: Taken together, we would like to suggest the use of Vit C supplementation as a safe, inexpensive, and effective strategy for the management of CUMS.

Unveiling the Therapeutic Potential of Small Molecule of SVAK-12: A Comprehensive In Silico, In Vitro, and In Vivo Studies on its Neuroprotective Effects and Molecular Interactions in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic cells and as of now, there is no established definitive treatment available for this condition. In this study, the focus was on investigating the impact of SVAK-12, a small molecule that can cross the blood-brain barrier and remain stable without structural changes. The effect of SVAK-12 was investigated in vitro on neurotoxicity, in vivo model of Parkinson's Diseases and in silico. Through in vitro and in vivo experiments, as well as molecular docking simulations, it was found that SVAK-12 (375 ng.ml) led to increased cell viability, reduced cellular damage, and decreased production of NO and ROS. Additionally, it boosted levels of important neurotrophic factors like BDNF (130.49%) and GDNF (116.38%), potentially aiding in alleviating motor disability and depression. The study also highlighted SVAK-12's potential as a therapeutic candidate for neurological disorders due to its ability to increase tyrosine hydroxylase expression and dopamine levels (4.84 times). While it did not significantly improve motor symptoms in vivo, it did enhance motor asymmetry in the forelimbs and gene expression related to brain regions. Besides, it induced significant BMP-2 gene expression in substantial nigra regions without significant changes in GDNF and Nurr1 gene expression in the striatum expression. The docking of SVAK-12, Levodopa, Amantadine, Biperiden, Selegiline, and Rasagiline to the binding site of GFRα1, sortilin, and TrkB showed that SVAK-12 had greater MolDock score than Selegiline and Amantadine for GFRα1 and greater than amantadine for Sortilin and TrKB. Overall, the study suggests that SVAK-12's neuro-biocompatibility, ability to reduce free radicals, and enhanced neurotrophic factors make it a promising candidate as a neuroprotective drug.

Intervention effects of Naoxintong capsules on psychological and cardiac status in depressed rats after heart failure

Abstract Background Depression is a common clinical phenomenon in the patients with heart failure (HF). In traditional Chinese medicine (TCM), diseases in the brain and heart are thought to be correlated and interact. Naoxintong capsules (NXT) has been used for treating cardio-cerebrovascular diseases, while its therapeutic effect on depression after HF remains unclear. Objective The aim of the study is to evaluate the intervention effect of NXT on depression after HF. Methods Sprague-Dawley rats were assigned into the following 5 groups: sham, model, NXT (250, 1000 mg/kg), and valsartan (8 mg/kg). Coronary artery occlusion was performed to induce HF and subsequent depression in rats. The cardiac function was evaluated by echocardiography, hematoxylin-eosin staining, and Masson trichrome staining. The sucrose preference test and Morris water maze test were carried out to assess the depressive behaviors in rats. The ultrastructure of hippocampal CA1 neurons was observed and the levels of corticotropin-releasing hormone in the hypothalamus, brain-derived neurotrophic factor in the cortex, and adrenocorticotropic hormone (ACTH) in the plasma were determined by enzyme-linked immunosorbent assay. The levels of dopamine, 5-hydroxytryptamine, norepinephrine, and γ-aminobutyric acid in the hippocampus were measured by UPLC-QQQ-MS. Results NXT reduced myocardial injury and pathological changes in the cardiac tissue and increased the left ventricular ejection fraction, left ventricular fractional shortening, and cardiac output. NXT increased the sugar preference rate and number of crossings and shortened the escape latency. Furthermore, the NXT treatment restored the levels of corticotropin-releasing hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, dopamine, and γ-aminobutyric acid to the baseline values. Conclusions NXT not only demonstrates cardioprotective effect but also attenuates depression in the rats after HF. It may exert the antidepressant effect by inhibiting the hyperactivity of the hypothalamic-pituitary-adrenal axis and recovering the levels of neurotrophic factors and neurotransmitters.

Effects of Boron on Learning and Behavioral Disorders in Rat Autism Model Induced by Intracerebroventricular Propionic Acid.

Autism spectrum disorder is a neurodevelopmental disorder in which learning, communication, and social interaction are impaired. Research has sought to minimize the neural impairments associated with autism spectrum disorder and improve the quality of life. Recent studies suggest that boron may benefit nerve cells, with effects varying depending on the dosage. This study explored the impact of boron, administered as boric acid, on behavioral, biochemical, and histopathological parameters in a rat model of autism induced by propionic acid (PPA). Thirty-two male Sprague-Dawley rats were divided into control, autism model, and boron-treated groups. Behavioral tests were conducted pre- and post-PPA induction, with brain tissue analyzed post-euthanasia. Proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6)) and brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus. Histopathological evaluations were conducted on the hippocampus and cerebellum. Autism model rats displayed impaired learning, elevated BDNF and cytokine levels, microglial and astrocytic activation, and decreased Purkinje cell count. The boron-treated groups showed improvements, particularly with the 4mg/kg dose. This dose enhanced learning and social interaction, reduced proinflammatory cytokine levels, prevented microglial and astrocytic activation, and increased Purkinje cell count. Boron treatment exhibited neuroprotective potential, ameliorating autism spectrum disorder deficits by modulating cytokines, BDNF, microglia, and astrocytes, with low doses yielding pronounced effects.

Obesity Control and Supplementary Nutraceuticals as Cofactors of Brain Plasticity in Multiple Sclerosis Populations.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in the MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS can provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for the MS population.

Ultra-processed foods intake in relation to metabolic health status, serum brain-derived neurotrophic factor and adropin levels in adults

BackgroundIn recent years, there has been a lot of discussion over the impact of ultra-processed foods (UPFs) intake on overall health of subjects. However, the association between UPFs intake and metabolic unhealthy (MU) status is still in a state of ambiguity. The current study assessed the relationship between UPFs intake and MU status with regard to brain-derived neurotrophic factor (BDNF) and adropin levels.MethodsA sample of Iranian adults (aged 20–65 years) was selected to participate in this cross-sectional study using a multistage cluster random-sampling method. UPFs intake was assessed by a validated food frequency questionnaire and NOVA classification. Concentrations of metabolic parameters, BDNF and adropin were determined through fasting blood samples. MU status was assessed according to the criteria proposed by Wildman.ResultsThe overall prevalence of MU phenotype among study participants (n = 527) was 42.5%. Higher intake of UPFs was associated with elevated odds of MU status in multivariable-adjusted model (ORT3 vs. T1=1.88; 95%CI: 1.02–3.45). Moreover, a positive association was observed between UPFs intake and hypertriglyceridemia after controlling all confounders (ORT3 vs. T1=2.07; 95%CI: 1.15–3.73). However, each tertile increase in UPFs intake was not significantly associated with serum BDNF (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\beta\\:$$\\end{document}=0.15; 95%CI: -0.05, 0.34; P = 0.14) and adropin (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\beta\\:$$\\end{document}=-1.37; 95%CI: -6.16, 3.42; P = 0.58) levels in multivariable-adjusted linear regression models.ConclusionOur findings suggested that higher consumption of UPFs was related to increased likelihood of MU status among a sample of Iranian adults. Further longitudinal studies are needed to verify the directionality and generalizability of the results to all adult populations.

7345 Study on the correlation between the levels of myokines and metabolic abnormality in obese children

Abstract Disclosure: L. Ouyang: None. M. Li: None. F. Yang: None. Objective: There are limited drug options to treat childhood obesity. Studies have found that myokines play an important role in the mechanism of exercise in the treatment of obesity. However, the correlation between myokines and metabolic abnormalities in obese children is still unclear. The purpose of this study is to analyze the correlation between the levels of myokines and metabolic abnormalities in obese children to provide the basis for the future application of myokines in childhood obesity. Methods: 41 obese children who visited the pediatric clinic of our hospital from March to October 2022 were enrolled, and 11 healthy non-obese children who had a regular physical examination in the pediatric clinic during the same period were enrolled. Basic information, anthropological indicators and biochemical indicators were collected. Human myokine magnetic bead panel was used to detect serum myokine levels including irisin, FGF21, BDNF, LIF, MSTN, IL 6, and IL 15. Difference analysis, rank sum test and Spearman analysis were used to conduct the correlation between the levels of myokines and metabolic abnormalities in obese children. Results: We found that the BMI-SDS and body fat rate of obese children with abnormal metabolism was higher than those with normal metabolism status(p&amp;lt;0.05). Children with abnormal glucose metabolism had an increased risk of abnormal lipid metabolism and hyperuricemia(p &amp;lt; 0.05), and children with abnormal lipid metabolism had an increased risk of hyperuricemia and hypertension(p&amp;lt;0.05). The obese children with abnormal glucose and lipid metabolism had an increased risk of abnormal purine metabolism. The levels of leukemia inhibitory factor and brain-derived neurotrophic factor in obese children were significantly higher than those in non-obese children (p&amp;lt;0.05), and the level of fibroblast growth factor 21 in obese children with abnormal metabolism was significantly higher than that in children with normal metabolism (p&amp;lt;0.05), respectively. There was a significant positive correlation between BMI-SDS and the levels of irisin, leukemia inhibitory factor and brain-derived neurotrophic factor (r=0.361, 0.368, 0.343, p=0.009, 0.007, 0.013, respectively). There was a significant positive correlation between irisin, BDNF, LIF, MSTN and IL 6, and between FGF21 and irisin, MSTN, IL 6 in children (p &amp;lt; 0.05). Conclusions: With the increase in BMI, the risk of metabolic abnormalities in obese children increases. Obese children with one kind of metabolic abnormality are prone to merge with other metabolic abnormalities. The levels of leukemia inhibitory factor, fibroblast growth factor 21, irisin, brain-derived neurotrophic factor, and other myokine in obese children and obese children with abnormal metabolism are different from those in non-obese children and obese children with normal metabolism respectively, and there is interaction between myokines. Presentation: 6/1/2024

Association Between Dietary Magnesium Intake with Serum Brain-Derived Neurotrophic Factor (BDNF) and Adropin Levels and Metabolic Health Status in Iranian Adults.

Given the sparse conclusive findings regarding the association of magnesium intake with metabolic health status and limited evidence relating magnesium intake to metabolic biomarkers, our objective was to evaluate the association of metabolic health status, adropin, and brain-derived neurotrophic factor (BDNF) in relation to dietary magnesium intake. In this cross-sectional study, 527 male and female adults were investigated in Isfahan City. The data regarding usual dietary intakes were gathered using a valid and reliable 168-item food frequency questionnaire. Biochemical variables, anthropometric indices, and blood pressure were assessed following standard methods. The criteria suggested by Wildman et al. were used to classify participants as metabolically unhealthy (MU) and metabolically healthy (MH). Moderate magnesium intake was associated with 71% reduced odds of MU (OR T2 vs. T1 = 0.29; 95% CI: 0.12-0.70). In the stratified analysis, the inverse association between moderate intake of magnesium and MU was seen only in overweight/obese subjects but not in normal-weight ones. A significant difference was found in serum levels of adropin between the first and second tertile of dietary magnesium intake among overweight/obese subjects (62.74 ± 4.99 vs. 50.13 ± 2.54, P = 0.03). After adjustment for potential covariates, this association became attenuated (59.06 ± 3.47 vs. 50.02 ± 3.64, P = 0.20). No statistically significant link was obtained between dietary intake of magnesium and circulating BDNF levels. Moderate dietary intake of magnesium may exert beneficial effects on metabolic health and serum levels of adropin, especially in obese/overweight individuals. Further prospective studies will be required to approve our findings.

New insights into individual differences in response to chronic unpredictable mild stress (CUMS) in rats with respect to hippocampal BDNF and GSK3-β expression levels

Preclinical and clinical studies have shown a wide-range of individual differences in response to stressors or novel environments which can affect the susceptibility to develop abnormal behaviors and neuropsychiatric disorders. Both vulnerability and resiliency have been observed in animals and humans experiencing stressful events. Chronic unpredictable mild stress (CUMS) is a rodent depression model consisting of various stressors. This protocol leads to depressive- and anhedonic-like behaviors in rodents. The present study aimed to evaluate potential individual differences in response to CUMS in rats, with respect to the expression level of brain-derived neurotrophic factor (BDNF) and glycogen synthase kinases 3-beta (GSK3-β) (proteins involved in the modulation of mood, neuroplasticity, and cognition) in the hippocampus. CUMS was performed for four consecutive weeks. Depressive-like behavior, locomotor activity, anxiety-like behavior, and pain threshold were also evaluated using forced swim test (FST), open field test (OFT), and the hot plate (HP), respectively. Real-time PCR was used to evaluate BDNF and GSK3-β expression levels. The results showed that CUMS rats can be classified as two clusters: affected and non-affected (depressed and non-depressed). Affected rats showed depressive- and anxiety-like behaviors, decreased locomotor activity, and increased pain threshold. However, non-affected rats were similar to controls. In addition, there was a downregulation of BDNF and upregulation of GSK3-β in affected rats. Spearman correlation analysis also showed a relationship between BDNF and GSK3-β expression levels with individual differences. In conclusion, the present study showed that BDNF and GSK3-β may be involved in individual differences in CUMS rats.

Lindera aggregata improves intestinal function and alleviates depressive behaviors through the BDNF/TrkB/CREB signaling pathway induced by CUMS in mice

Depression is a common mental illness, which is highly related to intestinal motor dysfunction and causes a global burden of disease. Lindera aggregata (LA), a traditional medicinal herb, has been used to treat gastrointestinal disorders; however, the effect of LA on depression remains unclear. Here, we assessed the impact of LA on chronic unpredictable mild stress (CUMS)-induced depression in mice and explored the related mechanisms. The results showed that LA ameliorated depressive behaviors in mice exposed to CUMS, as evidenced by improved performance in the sucrose preference test, force swimming test, and open field test, as well as increased serum levels of adrenocorticotropic hormone and 5-hydroxytryptamine. In addition, LA increased the serum levels of D-xylose and ghrelin, indicating that LA can promote gastrointestinal motility. Additional studies revealed that LA relieved CUMS-induced hippocampal tissue damage, as shown by hematoxylin and eosin and Nissl staining. LA increased the expression levels of brain-derived neurotrophic factor (BDNF) and promoted the activation of tropomyosin receptor kinase B (TrkB) and cAMP response element-binding (CREB) in the hippocampus of CUMS-exposed mice or in corticosterone-injured HT22 cells. In conclusion, LA can improve CUMS-induced depressive behavior in mice, potentially through hippocampal neuroprotection mediated by the BDNF/TrkB/CREB signaling pathway, which also contributes to improved intestinal function.

Neuroprotective effects of punicalagin and/or micronized zeolite clinoptilolite on manganese-induced Parkinson's disease in a rat model: Involvement of multiple pathways.

Manganism, a central nervous system dysfunction correlated with neurological deficits such as Parkinsonism, is caused by the substantial collection of manganese chloride (MnCl2) in the brain. To explore the neuroprotective effects of natural compounds, namely, micronized zeolite clinoptilolite (ZC) and punicalagin (PUN), either individually or in combination, against MnCl2-induced Parkinson's disease (PD). Fifty male albino rats were divided into 5 groups (Gps). Gp I was used as the control group, and the remaining animals received MnCl2 (Gp II-Gp V). Rats in Gps III and IV were treated with ZC and PUN, respectively. Gp V received both ZC and PUN as previously reported for the solo-treated plants. ZC and/or PUN reversed the depletion of monoamines in the brain and decreased acetyl choline esterase activity, which primarily adjusted the animals' behavior and motor coordination. ZC and PUN restored the balance between glutamate/γ-amino butyric acid content and markedly improved the brain levels of brain-derived neurotrophic factor and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and decreased glycogen synthase kinase-3 beta activity. ZC and PUN also inhibited inflammatory and oxidative markers, including nuclear factor kappa-light-chain-enhancer of activated B cells, Toll-like receptor 4, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 and caspase-1. Bcl-2-associated X-protein and B-cell leukemia/lymphoma 2 protein (Bcl-2) can significantly modify caspase-3 expression. ZC and/or PUN ameliorated PD in rats by decreasing the levels of endoplasmic reticulum (ER) stress markers (p-protein kinase-like ER kinase (PERK), glucose-regulated protein 78, and C/EBP homologous protein (CHOP)) and enhancing the levels of an autophagy marker (Beclin-1). ZC and/or PUN mitigated the progression of PD through their potential neurotrophic, neurogenic, anti-inflammatory, antioxidant, and anti-apoptotic activities and by controlling ER stress through modulation of the PERK/CHOP/Bcl-2 pathway.