Neurotrophic Factor Levels Research Articles

The effect of oyster mushroom (Pleurotus ostreatus) beta-glucan extract on brain -derived neurotrophic factor and neuron in high-fat-high-fructose diet-induced male Sprague Dawley rats

Obesity is a condition where there is an accumulation of excess body fat, which can increase oxidative stress either in the blood or in tissues, such as brain tissue. This situation can trigger atrophy in neurons and reduce brain-derived neurotrophic factor (BDNF) levels, which can increase the risk of impaired cognitive function. This study aimed to ascertain the effect of oyster mushroom (Pleurotus ostreatus) β-glucan extract on the number of neurons and levels of BDNF in rats. The study design was a true experimental with a randomized control group post-test only with white male Sprague Dawley rats as the subjects. A total of twenty-four rats were divided into four groups, namely the normal diet group fed AIN-93M standard diet (KN), the high-fat-high-fructose (HFHF) diet group (KP), and the HFHF diet group with the addition of β-glucan extract dose of 125 mg/kg body weight (P1), and dose of 375 mg/kg body weight (P2). The BDNF was measured by ELISA, and the number of neurons was by histological staining approach. Although there was no significant difference in the number of neurons (p = 0.692), the data revealed a significant difference in BDNF levels (p = 0.005). There was no relationship between the number of neurons and BDNF levels (p = 0.874) and between the β-glucan dose and the number of neurons (p = 0.796). However, there was a relationship between β-glucan dose and BDNF levels (p = 0.001; r = 0.695). This study concludes that the dose of β-glucan from oyster mushroom extract positively affects BDNF levels but not the number of neurons. There was no relationship between the number of neurons with BDNF levels and β-glucan dose. It was presumable because the staining technique was less specific, so the possibility of other cells counted as neurons may occur

Behavioral and Biochemical Effects of an Arylhydrazone Derivative of 5-Methoxyindole-2-Carboxylic Acid in a Scopolamine-Induced Model of Alzheimer’s Type Dementia in Rats

Alzheimer’s disease (AD) has long proven to be a complex neurodegenerative disorder, with cholinergic dysfunction, oxidative stress, and neuroinflammation being just a few of its pathological features. The complexity of the disease requires a multitargeted treatment covering its many aspects. In the present investigation, an arylhydrazone derivative of 5-methoxyindole-2-carboxylic acid (5MeO), with in vitro strong antioxidant, neuroprotective and monoamine oxidase B-inhibiting effects, was studied in a scopolamine-induced Alzheimer-type dementia in rats. Using behavioral and biochemical methods, we evaluated the effects of 5MeO on learning and memory, and elucidated the mechanisms of these effects. Our experiments demonstrated that 5MeO had a beneficial effect on different types of memory as assessed by the step-through and the Barnes maze tasks. It efficiently restored the decreased by scopolamine brain-derived neurotrophic factor and acetylcholine levels and normalized the increased by scopolamine acetylcholine esterase activity in hippocampus. Most effective 5MeO was in counteracting the induced by scopolamine oxidative stress by decreasing the increased by scopolamine levels of lipid peroxidation and by increasing the reduced by scopolamine catalase activity. Blood biochemical analyses demonstrated a favorable safety profile of 5MeO, prompting further pharmacological studies suggesting 5MeO as a safe and efficient candidate in a multitargeted treatment of AD.

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.

Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis.

Peripheral levels of brain-derived neurotrophic factor (BDNF) are often used as a biomarker for the rapid plasticity-promoting effects of ketamine, psychedelics, and other psychoplastogens in humans. However, studies analyzing peripheral BDNF after psychoplastogen exposure show mixed results. In this meta-analysis, we aimed to test whether the rapid upregulation of neuroplasticity seen in preclinical studies is detectable using peripheral BDNF in humans. This analysis was pre-registered (PROSPERO ID: CRD42022333096) and funded by the University of Fribourg. We systematically searched PubMed, Web of Science, and PsycINFO to meta-analyze the effects of all available psychoplastogens on peripheral BDNF levels in humans, including ketamine, esketamine, LSD, psilocybin, ayahuasca, DMT, MDMA, scopolamine, and rapastinel. Risk of bias was assessed using Cochrane Risk of Bias Tools. Using meta-regressions and mixed effects models, we additionally analyzed the impact of several potential moderators. We included 29 studies and found no evidence that psychoplastogens elevate peripheral BDNF levels in humans (SMD = 0.024, p = 0.64). This result was not affected by drug, dose, blood fraction, participant age, or psychiatric diagnoses. In general, studies with better-controlled designs and fewer missing values reported smaller effect sizes. Later measurement timepoints showed minimally larger effects on BDNF. These data suggest that peripheral BDNF levels do not change after psychoplastogen administration in humans. It is possible that peripheral BDNF is not an informative marker of rapid changes in neuroplasticity, or that preclinical findings on psychoplastogens and neuroplasticity may not translate to human subjects. Limitations of this analysis include the reliability and validity of BDNF measurement and low variation in some potential moderators. More precise methods of measuring rapid changes in neuroplasticity, including neuroimaging and stimulation-based methods, are recommended for future studies attempting to translate preclinical findings to humans.

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.

Transdiagnostic features of inflammatory markers and executive function across psychiatric disorders

Executive dysfunction and dysregulated inflammation are found in patients with different psychiatric disorders. However, whether there are different associations between inflammatory markers and executive performance in patients with different psychiatric diagnoses is unknown. Our study aims were (1) to compare peripheral cytokine expression and executive function in patients with bipolar disorder (BD), substance use disorder (SUD), and schizophrenia (SCZ), and in healthy controls (HC) and (2) to explore the potential association between inflammatory cytokines and executive function in different patient groups and HC. Participants with BD (n = 816), SUD (opioid use disorder and/or methamphetamine use disorder, n = 518), SCZ (n = 146), and HC (n = 186) were recruited. Plasma cytokine levels [tumor necrosis factor (TNF)-α, interleukin (IL)-8 (only measured in 8 SCZ patients), transforming growth factor (TGF)-β1 (not measured in SCZ patients)], C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF) levels, and executive function [Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT)] were assessed. We found that all patient groups had worse executive performance and higher inflammatory cytokine levels than the HC group. SCZ patients had the worst executive performance, while SUD patients had the highest inflammatory cytokine levels. Increased plasma IL-8, CRP, and TNF-α levels were specifically associated with worse executive function in BD, SUD, and SCZ patients (P = 0.009, 0.04, and 0.03, respectively). We concluded that dysregulated inflammation might be a transdiagnostic feature among different psychiatric disorders and associated with executive dysfunction. Further studies to investigate the causal relationship and mechanisms between inflammation and executive dysfunction may be needed.

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.

Does acupuncture combined with MOTOmed movement therapy have a better rehabilitation effect on post-stroke hemiplegia patients? A systematic review and meta-analysis

ABSTRACT Background Combinations of rehabilitation therapies are widely used in patients with post-stroke hemiplegia. A combination of acupuncture and MOTOmed had been shown to promote the recovery of post-stroke hemiplegia patients. We conducted a systematic review of evidence from studies that investigated the use of acupuncture combined with MOTOmed for rehabilitation of patients with post-stroke hemiplegia. Objective To estimate the rehabilitation effect of acupuncture combined with MOTOmed movement therapy in patients with post-stroke hemiplegia. Methods Randomized controlled trials (RCTs) of acupuncture combined with MOTOmed movement therapy in patients with post-stroke hemiplegia were retrieved from nine databases. Risk-of-bias assessments were conducted using the Cochrane Risk-of-bias Tool. Meta-analysis of outcome measures was performed using RevMan 5.4 software. And we followed the PRISMA 2020 guidelines. Results Eighteen studies involving 1637 participants were included. Compared with conventional rehabilitation, acupuncture, or MOTOmed movement therapy alone, acupuncture combined with MOTOmed movement therapy increased the scores of Fugl-Meyer Assessment Scale-lower extremity (FMA-LE), Berg Balance Scale (BBS), Functional Ambulation Categories scale (FAC), Maximal Walking Speed test (MWS), gait parameters of 3D gait analysis, Barthel Index (BI), Modified Barthel Index (MBI), total effective rate, and the levels of neurotrophic factors (NGF, BDNF and NT-3) in serum, while reduced the scores of Clinic Spasticity Index (CSI) and National Institutes of Health Stroke Scale-Lower Extremity (NIHSS-LE) (p < 0.05 for all). Conclusion Acupuncture combined with MOTOmed movement therapy has better efficacy than conventional rehabilitation, acupuncture, or MOTOmed alone in patients with post-stroke hemiplegia. This combination therapy can promote the rehabilitation of these patients.

Dynamic changes in the hippocampal memory index and biochemical indices in Sprague Dawley rats exposed to intrauterine kola nut

Kola nut is commonly consumed by pregnant women to suppress symptoms of morning sickness. This study investigated the effects of kola nut on the biochemical indices of the hippocampus and its dependent memory. Kola nut extract was fed to pregnant dams from the first day of their pregnancy until parturition. The following behavioral function tests were conducted: surface righting (SR); cliff avoidance (post-natal day [PND] 4, 5, 6 & 7); open field; novel object recognition and location; and radial-arm maze (PND 21 and 56). The levels of brain-derived neurotrophic factor (BDNF), acetylcholine (ACh), and malondialdehyde (MDA) of the matched hippocampal tissues were also checked in the pups. The kola nut-treated pups showed significantly reduced behavioral indices compared to the pups in the control group: lower postural balance, higher risk avoidance memory, and lower frequency in pivoting and rearing compared to that in the control group. However, the frequency of urine and fecal bolus was significantly lower in the pups in the control group than that in the treated pups. The discrimination ratio of the control group pups in novel object recognition (NOR) and novel object location (NOL) was significantly higher than that in the treated pups, and the time taken by the treated pups to complete RAM was significantly higher. The levels of ACh and BDNF in the treated pups were increased compared to that in control pups. A positive correlation was found between MDA and SR (r = 0.7207; p = 0.0437), grooming (r = 0.7707; p = 0.0252), and fecal bolus (r = 0.7606; p = 0.0284), as well as with the BDNF level in those treated with grooming (r = 0.7570; p = 0.0297). However, negative correlations between ACh and rearing (r = -0.8261; p = 0.0115) and fecal bolus (r = -0.8066; p = 0.0156) and a positive correlation with NOL (r = 0.8358; p = 0.0098) were observed. Based on these observations, the study concluded that Kola nut affects both biochemical and hippocampal memory profiles.

Activation of Hippocampal Neuronal NADPH Oxidase NOX2 Promotes Depressive-Like Behaviour and Cognition Deficits in Chronic Restraint Stress Mouse Model.

Nicotinamide adenosine dinucleotide phosphate oxidases (NOX) play important roles in mediating stress-induced depression. Three NOX isotypes are expressed mainly in the brain: NOX2, NOX3 and NOX4. In this study, the expression and cellular sources of these NOX isoforms was investigated in the context of stress-induced depression. Chronic restraint stress (CRS)-induced depressive-like behaviour and cognitive deficits were evaluated by tail suspension tests, forced swimming tests and the Morris water maze test. Hippocampal NOX expression was determined by immunofluorescence staining and western blotting. The hippocampal levels of the brain-derived neurotrophic factor (BDNF) mRNA were determined via quantitative real-time -polymerase chain reaction. Glucocorticoid levels in the hippocampus were measured using ELISA kits. In the mouse CRS model, a significant increase in NOX2 expression was observed in the hippocampus, whereas no significant changes in NOX3 and NOX4 expression were detected. Next, NOX2 expression was primarily localised to neurons (NeuN+) but not microglia (Iba-1+) or astrocytes (GFAP+). Treatment with gp91ds-tat, a specific NOX2 inhibitor, effectively mitigated the behavioural deficits induced by CRS. The decreased expression of the BDNF mRNA in the hippocampus of CRS mice was restored upon gp91ds-tat treatment. A positive correlation was identified between neuronal NOX2 expression and serum glucocorticoid levels. Our study indicated that neuronal NOX2 may be a critical mediator of depression-like behaviours and spatial cognitive deficits in mice subjected to CRS. Blockade of NOX2 signalling may be a promising therapeutic strategy for depression.

Serum and Oral Fluid Levels of Protein Markers and Hormones in Patients With Alcohol Dependence Syndrome

Background: The development of alcohol dependence syndrome is accompanied by disturbances of neuroplasticity in neural circuits, the imbalance of neurotransmitter metabolism and immune and hormonal statuses in the central nervous system, which are reflected in changes in peripheral markers. Therefore, determining neuropeptide levels in body fluids is a potentially promising strategy for laboratory monitoring of substance use.Objective: To determine characteristics of changes in oral fluid and serum levels of protein markers and hormones in patients with alcohol dependence syndrome during rehabilitation.Materials and methods: We formed 2 groups of male participants: a control group of apparently healthy volunteers (n = 30) and a group of patients with alcohol dependence syndrome, which was similar in size, age, and gender (20-40 years) to the controls. At the time of admission to the rehabilitation program and 3 months later, serum and oral fluid samples were collected. We used an enzyme-linked immunosorbent assay to determine levels of brain-derived neurotrophic factor (BDNF), glial cell line–derived neurotrophic factor, neuropeptide Y, orexin, pituitary adenylate cyclase-activating peptide, corticotropin, and cortisol in the body fluids.Results: Laboratory findings revealed that it is possible to determine neuropeptides and hormones in the oral fluid. The wide variability of findings in the oral fluid and no statistically significant correlation with corresponding serum levels were characteristic of the most protein markers. Only the BDNF levels were statistically significantly reduced (3.2-fold decrease) in both the serum and oral fluid. Analysis of the serum and oral fluid BDNF and cortisol levels revealed a moderate correlation (r = 0.51, P = .0189).Conclusions: For laboratory monitoring of alcohol dependence syndrome, it is possible to determine oral fluid BDNF, which, like cortisol, has demonstrated a statistically significant moderate correlation between the serum and oral fluid levels.

Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Epilepsy occurs in 35–95% of patients with low-grade malignant cerebral gliomas and in 29–71% of patients with high-grade gliomas. Seizures can be the first manifestation of a malignant cerebral glioma or may develop in the postoperative period and during chemoradiation therapy. This necessitates the use of antiepileptic drugs that can control seizures, ensure seizure prevention, and provide secondary seizure prophylaxis without reducing the effectiveness of anticancer therapy or the patient’s quality of life. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms, with glutamate playing a key role. Increased glutamate secretion is accompanied by elevated expression and activation of its receptors, which raises seizure susceptibility. This is associated with increased levels of brain-derived neurotrophic factor, the number of synapses between peritumoral neurons and glioma cells, and the expression of various growth factors, all of which contribute to tumor progression. In this context, special attention is given to perampanel, a glutamate receptor antagonist and third-generation antiepileptic drug, in the treatment of epilepsy in patients with malignant cerebral gliomas. It has been shown that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas but also suppresses tumor progression. Perampanel can dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. A synergistic effect of perampanel in combination with temozolamide has been identified. During chemoradiation therapy, perampanel exerts a protective effect on healthy peritumoral tissues. Adverse drug reactions associated with perampanel use are infrequent and mild. Further research is needed to investigate the anticonvulsant and antitumor efficacy of perampanel for the treatment of epilepsy in patients with malignant brain tumors.

ACSL3 is a promising therapeutic target for alleviating anxiety and depression in Alzheimer's disease.

Alzheimer's disease (AD), the leading cause of dementia, affects over 55 million people worldwide and is often accompanied by depression and anxiety. Both significantly impact patients' quality of life and impose substantial societal and economic burdens on healthcare systems. Identifying the complex regulatory mechanisms that contribute to the psychological and emotional deficits in AD will provide promising therapeutic targets. Biosynthesis of omega-3 (ω3) and omega-6 fatty acids (ω6-FA) through long-chain acyl-CoA synthetases (ACSL) is crucial for cell function and survival. This is due to ω3/6-FA's imperative role in modulating the plasma membrane, energy production, and inflammation. While ACSL dysfunction is known to cause heart, liver, and kidney diseases, the role of ACSL in pathological conditions in the central nervous system (e.g., depression and anxiety) remains largely unexplored. The impact of ACSLs on AD-related depression and anxiety was investigated in a mouse model of Alzheimer's disease (3xTg-AD). ACSL3 levels were significantly reduced in the hippocampus of aged 3xTg-AD mice (via capillary-based immunoassay). This reduction in ACAL3 was closely associated with increased depression and anxiety-like behavior (via forced swim, tail suspension, elevated plus maze, and sucrose preference test). Upregulation of ACSL3 via adenovirus in aged 3xTg-AD mice led to increased protein levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor C (VEGF-C) (via brain histology, capillary-based immunoassay), resulting in alleviation of depression and anxiety symptoms. The present study highlights a novel neuroprotective role of ACSL3 in the brain. Targeting ACSL3 will offer an innovative approach for treating AD-related depression and anxiety.

Peripheral molecular and brain structural profile implicated stress activation and hyperoxidation in methamphetamine use disorder.

Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction. In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme-linked immunosorbent assay. The overall molecular disruption caused by methamphetamine was inversely related to withdrawal time (P = 0.0008), with partial recovery observed after 1 year of follow-up (P = 2.20 × 10-5). Molecules related to stress, immune activation, oxidative products, and cardiac injury were significantly elevated in all MUD groups, while antioxidation enzymes were downregulated. Additionally, the blood level of brain-derived neurotrophic factor was significantly correlated with gray matter volumes in nine brain regions (fusiform gyrus, orbitofrontal cortex, temporal pole, caudate, cerebellum crus, and vermis, adjusted P < 0.05) among patients with MUD. These findings suggest that patients with MUD exhibit elevated levels of immune response, stress, and oxidative stress, which are associated with brain structural abnormalities.

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.

Exploring the mechanism of action of huoermai essential oil for plateau insomnia based on the camp/CREB/BDNF/gabaergic pathway

Ethnopharmacological relevanceThe traditional Huoermai therapy is a treatment for insomnia used by the Tibetan people living on the Tibetan plateau in China. This therapy involves the use of Myristica fragrans Houtt. and Carum carvi L., along with fomentation and massage, and has shown significant clinical effects. However, the mechanism of how Huoermai therapy treats plateau insomnia needs further clarification. Aim of the studyThis study aimed to investigate the mechanism of action of Huoermai essential oil (HEO) in treating plateau insomnia, focusing on the cAMP/CREB/BDNF/GABAergic pathway. MethodsThe major components of Huoermai essential oil were identified by Gas chromatography-mass spectrometry (GC-MS) for subsequent network pharmacology analysis. Proteomics techniques were employed to pinpoint disparities in brain tissue protein expression in a mouse model of plateau insomnia following Huoermai therapy administration, in conjunction with network pharmacology to forecast pathways related to hypoxia and insomnia. Plateau insomnia mouse model was established and the therapeutic impact of Huoermai essential oil was evaluated. Hematoxylin & Eosin staining(HE) was conducted to observe pathological damage to the cortex, hippocampus, thalamus and hypothalamus structures. Changes in serotonin (5-HT), melatonin (MT), adenosine (AD), cyclic adenosine monophosphate (cAMP) and malondialdehyde (MDA) levels in mouse brain tissue were gauged through enzyme-linked immunosorbent assay (ELISA) to assess sleep status and oxidative stress levels in mice. Molecular docking was employed to anticipate the target binding energy of Huoermai essential oil constituents. ELISA and Western Blot (WB) were used to ascertain the expression of cAMP/CREB/BDNF/GABAergic pathway. ResultsThe results indicated that HEO positively impacted intermittent hypobaric hypoxia-induced plateau insomnia in mice. Histological examination results showed that HEO ameliorated neuronal damage in specific regions of the brain affected by plateau insomnia, such as the cortex, hippocampus, thalamus, and hypothalamus. Through GC-MS analysis, 56 volatile oil components were identified. Subsequently, a combined network pharmacology and proteomics analyses led to selecting the cAMP/CREB/BDNF/GABAergic pathway for further study. ELISA experiments demonstrated that HEO treatment increased GABA and MT levels while significantly reducing 5-HT and adenosine levels in brain tissue of mice with plateau insomnia. WB results revealed that HEO ameliorated plateau insomnia by suppressing the hyperactivation of the cAMP pathway, increasing brain-derived neurotrophic factor (BDNF) levels and B-cell lymphoma-2 (BCL-2) expression, and alleviating hypoxia-induced oxidative stress. Moreover, molecular docking results showed strong binding affinity of all pharmacological components to their targets and proteins in the brain. ConclusionThese results indicate that HEO significantly prolongs sleep duration in plateau insomniac mice and treats plateau insomnia by modulating levels of sleep-related regulators, modulating the cAMP pathway, increasing GABA receptor expression, and improving neuronal survival and anti-apoptosis.

The Effect of Two Somatic-Based Practices Dance and Martial Arts on Irisin, BDNF Levels and Cognitive and Physical Fitness in Older Adults: A Randomized Control Trial.

Maintaining healthy brain function during ageing is of great importance, especially for the self-sufficiency of older adults. The main aim of this study was to determine the effects of dance and martial arts on exerkines Brain Derived Neurotrophic Factor (BDNF) and irisin blood serum levels. This randomized controlled trial examined the effects of dance and martial arts on serum Brain-Derived Neurotrophic Factor (BDNF) and irisin levels, as well as cognitive function, mood, and physical measures in older adults. Seventy-seven independently living older adults (mean age 70.3±3.8 years) were randomized into three groups: dance (DG), martial arts (MaG), and control (CG), followed over 12weeks. Generalized linear models were used to assess the interventions' effects. There was a significant increase in BDNF levels in both the DG (1.8 ± 4.9, p < 0.05) and MaG (3.5 ± 6.3, p < 0.05), while CG experienced a decrease (-4.9 ± 8.2, p < 0.05). Between-group effects were significant for BDNF, with DG and MaG showing higher levels than CG (p < 0.05). No significant changes in irisin levels were found. Cognitive performance, particularly attention and mental flexibility (measured by the Trail Making Test A and B), significantly improved in the DG compared to CG (p < 0.05). Additionally, participants in DG showed improved mood based on the Geriatric Depression Scale (p < 0.05) compared to CG. Anthropometric T-scores were significantly associated with changes in irisin levels (p < 0.05) after intervention. The study found that dance and martial arts upregulated BDNF levels, with dance showing notable improvements in cognitive function and mood in older adults. Changes in anthropometric measures were linked to increased irisin levels. These findings suggest that both dance and martial arts may promote healthy brain function in aging populations. NCT05363228.

Neonatal Maternal Separation Impairs Cognitive Function and Synaptic Plasticity in Adult Male CD-1 Mice

Maternal separation (MS) increases the risk of occurrence of anxiety, depression, and learning and memory impairment in offspring. However, the underlying molecular biological mechanisms remain unclear. In the current study, offspring CD-1 mice were separated from their mothers from postnatal day 4 to postnatal day 21. At 3 months of age, the male offspring were selected for the evaluation of anxiety- and depression-like behaviors and learning and memory function. Western blotting and RT-PCR were used to examine the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin. Long-term potentiation (LTP) and long-term depression (LTD) were recorded at Schaffer collateral/CA1 synapses. Furthermore, basal synaptic transmission was evaluated via the recording of the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). The results showed that adult offspring CD-1 mice displayed anxiety- and depressive-like behaviors as well as impaired spatial learning and memory abilities. Electrophysiological analysis indicated that MS impaired LTP, enhanced LTD, and reduced the frequency of mEPSCs in pyramidal neurons in the CA1 region. Our findings suggested that MS can lead to anxiety, depression, and cognitive deficits, and these effects are associated with alterations in the levels of synaptic plasticity-associated proteins, consequently, also synaptic plasticity.

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.