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The prevalence of Alzheimer's disease (AD) is on the rise globally, and everyone who develops AD eventually experiences mild cognitive impairment (MCI) first. Timely intervention at an early stage of the disease may mitigate disease progression. Recent studies indicate that BDNF and MMP-9 play a significant role in the pathogenesis of AD. Therefore, this study aims to ascertain whether there are differences in plasma BDNF and MMP-9 levels between individuals with mild cognitive impairment due to AD and those with normal cognition, and to analyze the factors influencing mild cognitive impairment.This case-control study included 102 individuals with mild cognitive impairment and 102 controls, matched by age and sex. Participants completed a series of questionnaires, neuropsychological assessments, and clinical examinations. Plasma concentrations of BDNF and MMP-9 of the participants were quantified using ELISA. Subsequently, the factors influencing MCI were analyzed using univariate and multivariate logistic regression. The differences in plasma BDNF levels, MOCA total scores, and scores in various cognitive domains (including visuospatial and executive abilities, abstract thinking, attention, language, naming, and delayed memory) between the MCI and the control groups showed statistically significant (p < 0.05). Logistic regression analysis revealed that plasma BDNF levels and years of formal education were significantly negatively associated with MCI. This study indicates that plasma BDNF and years of formal education are protective factors influencing cognitive function. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is a neuropsychiatric condition whose neurobiological characteristics include alterations in brain plasticity, modulated by Brain-Derived Neurotrophic Factor (BDNF). In animal models, environmental enrichment promotes neuroplasticity and reduces depressive-like behaviors. In humans, we proposed to assess the level of Enriched Environment (EE) using a questionnaire that includes different domains of the EE (cognitive, social, and physical), which we named the EE Indicator (EEI). Objective: To determine the relationship between the level of EE and serum BDNF in participants with MDD and healthy controls. Materials: Participants with MDD without antidepressant treatment and healthy controls were recruited, and their EE level and serum BDNF concentration were determined looking for correlations between their clinical characteristics and the cognitive, social, and physical activities according to the EEI. Results: A total of 25 participants were recruited, of which 6 participants with MDD and the same number of controls were selected in a paired manner. Although no differences were found in the concentration of BDNF between the groups, positive correlations were observed between cognitive EE and BDNF (r = 0.62, p = 0.035), as well as negative social EE and the Hamilton Depression Rating Scale (HDRS) (r = −0.86, p = 0.001). The sum between cognitive and social EE showed a positive correlation with the serum concentration of BDNF (r = 0.34, p = 0.0451). Conclusions: The level of EE is potentially modulating the presence and severity of MDD at a clinical level, but it can also influence at a neuroplastic level through promoting or limiting the concentration of BDNF. [ABSTRACT FROM AUTHOR]

Background: Asiaticoside, the main active ingredient of Centella asiatica, is a pentacyclic triterpenoid compound. Previous studies have suggested that asiaticoside possesses neuroprotective and anti-depressive properties, however, the mechanism of its anti-depressant action not fully understood. In recent years, a growing body of research on anti-depressants has focused on the microbiota-gut-brain axis, we noted that disruption of the gut microbial community structure and diversity can induce or exacerbate depression, which plays a key role in the regulation of depression. Methods: Behavioral experiments were conducted to detect depression-like behavior in mice through sucrose preference, forced swimming, and open field tests. Additionally, gut microbial composition and short-chain fatty acid (SCFA) levels in mouse feces were analyzed 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5-HT1A) expression in mice was assessed by western blotting. Changes in serum levels of inflammatory factors, neurotransmitters, and hormones were measured in mice using ELISA. Results: This study revealed that oral administration of asiaticoside significantly improved depression-like behavior in chronic unpredictable mild stress (CUMS) mice. It partially restored the gut microbial community structure in CUMS mice, altered SCFA metabolism, regulated the hypothalamic-pituitary-adrenal axis (HPA axis) and inflammatory factor levels, upregulated BDNF and 5-HT1A receptor protein expression, and increased serum serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal that asiaticoside exerts antidepressant effects via the microbiota-gut-brain axis. Conclusions: These results suggested that asiaticoside exerts antidepressant effects through the microbiota-gut-brain axis in a CUMS mouse model. [ABSTRACT FROM AUTHOR]

Background and Aim: The prevalence of overweight and obesity is increasing dramatically due to unhealthy lifestyles. This study aimed to determine the effects of six weeks of total-body resistance exercise (TRX) combined with purslane supplementation on serum levels of brain-derived neurotrophic factor (BDNF), adropin, and nesfatin in overweight girls. Methods: In this semi-experimental study, 32 overweight female students aged 16 to 18 years (BMI > 25) from Ganaveh County, Bushehr Province, Iran, were randomly selected. The participants were divided into four groups: exercise, supplement, exercise + supplement, and placebo. The exercise groups performed TRX exercises consisting of 9 to 11 movements for six weeks, with three sessions per week, each lasting 60 minutes. Purslane supplementation was administered as two 500 mg capsules of purslane (Perpin Ala) taken daily after breakfast and lunch. Serum levels of BDNF, adropin, and nesfatin were measured using ELISA at the beginning and end of the six-week study. Results: The serum levels of BDNF in the exercise + supplement group showed significant differences compared to the exercise, supplement, and control groups (P < 0.05). Additionally, the serum levels of nesfatin were significantly different between the exercise + supplement group and the control group (P < 0.05). However, there were no significant differences in serum levels of adropin among the groups (P > 0.05). Conclusion: The findings suggest that a combination of TRX exercises and purslane supplementation over six weeks positively affects BDNF and nesfatin levels in young girls, potentially aiding in weight reduction. Further research is needed to explore this area more comprehensively.

Background: Impulsivity assessment may serve as a valuable clinical tool in the stratification of suicide risk. Acting without forethought is a crucial feature in the psychopathology of many psychiatric disturbances and corresponds with suicidal ideations, behaviors, and attempts. Methods: We present data on biological and psychological correlates of impulsivity among young adults (n = 47). Psychological analysis included both the self-description questionnaire—Barratt Impulsiveness Scale (BIS-11)—and neuropsychological behavioral tests, including the Iowa Gambling Task (IGT), the Simple Response Time task (SRT), and the Continuous Performance Test (CPT). mRNA and micro-RNA were isolated from peripheral blood mononuclear cells (PBMC). Expression levels of Brain-Derived Neurotrophic Factor (BDNF) mRNA and its regulatory micro RNAs, mir-1-3p, mir-15a-5p, mir-26a-5p, mir-26b-5p, and mir-195-5p, were analyzed using the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. proBDNF and BDNF plasma protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Significant correlations between BDNF mRNA and mir-15a-5p as well as proBDNF levels and mir-1-3p were detected. proBDNF protein levels correlated with motor and perseverance, while mir-26b correlated with cognitive complexity subdimensions of the BIS-11 scale. Correlations between BDNF, miRNAs, and the results of neuropsychological tests were also detected. Conclusions: The BDNF pathway shows a clinical potential in searching for biomarkers of impulse-control impairment. BDNF-regulatory micro-RNAs are detectable and related to clinical parameters in the studied population, which needs further research. [ABSTRACT FROM AUTHOR]

Early developmental malnutrition exerts adverse effects on the structural, neurochemical, and neurophysiological maturation of cerebral cells by disrupting the process of neurogenesis. Pasak bumi (Eurycoma longifolia Jack) and seluang fish (Rasbora spp.), two indigenous natural resources of South Kalimantan, Indonesia, are believed to harbor nutritional components capable of mitigating these deleterious effects. We aimed to assess the impact of administering pasak bumi, seluang fish, and pure docosahexaenoic acid (DHA) on the neurogenesis process in malnourished rat models. The Rattus norvegicus specimens were partitioned into seven distinct cohorts, each consisting of five rats: healthy rats in the negative control group (KN), while malnourished rats in the positive control (KP) and treatment groups (P1, P2, P3, P4, and P5). Both the KP and KN groups received a placebo and a standard feed. The treatment groups received different interventions for five weeks: standard feed alongside pasak bumi extract for the P1 group, standard feed and DHA for the P2 group, standard feed in combination with pasak bumi extract and DHA for the P3 group, seluang fish for the P4 group, and pasak bumi extract and seluang fish for the P5 group. The doses determined for the pasak bumi extract and DHA were 15 and 1 mg/kg bw, respectively. The parameters evaluated consisted of the levels of brain-derived neurotrophic factor (BDNF), neural progenitor cell β-tubulin 3 (Tuj-1) expression, and peroxisome proliferator-activated receptor gamma (PPARγ). The data were subjected to analysis through the Kruskal-Wallis test and analysis of variance (ANOVA) at a 95% confidence level. A value of p<0.05 was considered significant. Statistically significant differences were observed in the BDNF levels (p=0.00) and Tuj-1 expressions (p=0.01) across all groups. In conclusion, the combined administration of pasak bumi and seluang fish demonstrates the capacity of enhancing neurogenesis in malnourished rats, as evidenced by elevated BDNF levels and Tuj-1 expressions. [ABSTRACT FROM AUTHOR]

Neurotrophic factors play pivotal roles in shaping brain development and function, with brain-derived neurotrophic factor (BDNF) emerging as a key regulator in various physiological processes. This review explores the intricate relationship between BDNF and anorexia nervosa (AN), a complex psychiatric disorder characterized by disordered eating behaviors and severe medical consequences. Beginning with an overview of BDNF's fundamental functions in neurodevelopment and synaptic plasticity, the review delves into recent clinical and preclinical evidence implicating BDNF in the pathophysiology of AN. Specifically, it examines the impact of BDNF polymorphisms, such as the Val66Met variant, on AN susceptibility, prognosis, and treatment response. Furthermore, the review discusses the interplay between BDNF and stress-related mood disorders, shedding light on the mechanisms underlying AN vulnerability to stress events. Additionally, it explores the involvement of BDNF in metabolic regulation, highlighting its potential implications for understanding the metabolic disturbances observed in AN. Through a comprehensive analysis of clinical data and animal studies, the review elucidates the nuanced role of BDNF in AN etiology and prognosis, emphasizing its potential as a diagnostic and prognostic biomarker. Finally, the review discusses limitations and future directions in BDNF research, underscoring the need for further investigations to elucidate the complex interplay between BDNF signaling and AN pathology. [ABSTRACT FROM AUTHOR]

Neurotrophins are important regulators of neuronal and non-neuronal functions. As such, the neurotrophins and their receptors, the tropomyosin receptor kinase (Trk) family of receptor tyrosine kinases, has attracted intense research interest and their role in multiple diseases including Alzheimer's disease has been described. Attempts to administer neurotrophins to patients have been reported, but the clinical trials have so far have been hampered by side effects or a lack of clear efficacy. Thus, much of the focus during recent years has been on identifying small molecules acting as agonists or positive allosteric modulators (PAMs) of Trk receptors. Two examples of successful discovery and development of PAMs are the TrkA-PAM E2511 and the pan-Trk PAM ACD856. E2511 has been reported to have disease-modifying effects in preclinical models, whereas ACD856 demonstrates both a symptomatic and a disease-modifying effect in preclinical models. Both molecules have reached the stage of clinical development and were reported to be safe and well tolerated in clinical phase 1 studies, albeit with different pharmacokinetic profiles. These two emerging small molecules are interesting examples of possible novel symptomatic and disease-modifying treatments that could complement the existing anti-amyloid monoclonal antibodies for the treatment of Alzheimer's disease. This review aims to present the concept of positive allosteric modulators of the Trk receptors as a novel future treatment option for Alzheimer's disease and other neurodegenerative and cognitive disorders, and the current preclinical and clinical data supporting this new concept. Preclinical data indicate dual mechanisms, not only as cognitive enhancers, but also a tentative neurorestorative function. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that causes physical damage to neuronal connections, leading to brain atrophy. This disruption of synaptic connections results in mild to severe cognitive impairments. Unfortunately, no effective treatment is currently known to prevent or reverse the symptoms of AD. The aim of this study was to investigate the effects of three synthetic peptides, i.e., KLVFF, RGKLVFFGR and RIIGL, on an AD in vitro model represented by differentiated SH-SY5Y neuroblastoma cells exposed to retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). The results demonstrated that RIIGL peptide had the least significant cytotoxic activity to normal SH-SY5Y while exerting high cytotoxicity against the differentiated cells. The mechanism of RIIGL peptide in the differentiated SH-SY5Y was investigated based on changes in secretory proteins compared to another two peptides. A total of 380 proteins were identified, and five of them were significantly detected after treatment with RIIGL peptide. These secretory proteins were found to be related to microtubule-associated protein tau (MAPT) and amyloid-beta precursor protein (APP). RIIGL peptide acts on differentiated SH-SY5Y by regulating amyloid-beta formation, neuron apoptotic process, ceramide catabolic process, and oxidative phosphorylation and thus has the potentials to treat AD. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) plays a vital role in supporting neuronal survival, differentiation, and promoting synaptogenesis, thereby facilitating synaptic plasticity in the central nervous system. Administration of exogenous BDNF is a crucial approach for treating central nervous system injuries. However, the inability of sustained drug release to match disease activity often leads to insufficient drug accumulation in the injured area (ineffectiveness) and severe side effects induced by the drug (toxicity). Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are typically upregulated after tissue damage, and their upregulated expression levels represent the degree of disease activity. In this study, we utilized bioengineering techniques to prepare a BDNF that can specifically bind to collagen and be released in response to MMP substrate cleavage (collagen binding domain tissue inhibitor of matrix metalloproteinases brain-derived neurotrophic factor, CBD-TIMP-BDNF). We verified the ability of CBD-BDNF and CBD-TIMP-BDNF to specifically bind to collagen through collagen binding experiments, examined the characteristics of CBD-TIMP-BDNF in response to MMP-2 to release BDNF, and detected the biological activities of both recombinant proteins. The results demonstrated that the established microenvironment-controlled BDNF release system can respond to MMP-2 to release BDNF. The recombinant proteins CBD-BDNF and CBD-TIMP-BDNF exhibited similar biological activities to the BDNF standard. Targeting the upregulated expression of MMPs after spinal cord injury as a trigger for drug release, it is expected to achieve on-demand release of BDNF in response to the severity of the disease. [ABSTRACT FROM AUTHOR]

The brain-derived neurotrophic factor (BDNF) plays a crucial role during neuronal development as well as during differentiation and synaptogenesis. They are important proteins present in the brain that support neuronal health and protect the neurons from detrimental signals. The results from the present study suggest BDNF expression can be increase up to ~8-fold by treating the neuroblastoma cells SHSY-5Y with an herbal extract of Oroxylum indicum (50 μg/mL) and ~5.5-fold under lipopolysaccharides (LPS)-induced inflammation conditions. The Oroxylum indicum extract (Sabroxy) was standardized to 10% oroxylin A, 6% chrysin, and 15% baicalein. In addition, Sabroxy has shown to possess antioxidant activity that could decrease the damage caused by the exacerbation of radicals during neurodegeneration. A mode of action of over expression of BDNF with and without inflammation is proposed for the Oroxylum indicum extract, where the three major hydroxyflavones exert their effects through additive or synergistic effects via five possible targets including GABA, Adenoside A2A and estrogen receptor bindings, anti-inflammatory effects, and reduced mitochondrial ROS production. [ABSTRACT FROM AUTHOR]

Seizure is known to induce oxidative stress which may initiate neuronal death. Oxidant-antioxidant imbalance often leads to mitochondrial dysfunction, inflammation, and apoptosis in the brain which may further result in the development of seizure. Phenolic compounds such as curcumin and rosmarinic acid are reported to control convulsions and seizures in pentylenetetrazol induced seizures models by suppressing seizure time, oxidative stress and inflammation indirectly. Sinapic acid (SA), a polyphenolic product of hydroxycinnamic acid found in various plants, exhibits anti-inflammatory, antioxidant and anxiolytic effects. In this study, we investigated the effects of sinapic acid on pentylenetetrazol induced seizures in rats through oxidative stress, inflammation, apoptosis, and neurotrophic factor. A total of 28 male Wistar Albino rats weighing 200-220 g were divided into four equal groups (n=7/group). The treatment groups received 10 mg/kg and 20 mg/kg SA, respectively, by oral gavage for five consecutive days along with pentylenetetrazol (45 mg/kg, intraperitoneal) to induce seizures. The levels of Total oxidant status (TOS), Total antioxidant status (TAS), TNF-α, IL-1β, and Brain-derived neurotrophic factor (BDNF) were measured in the cortex and hippocampus. Additionally, caspase 3 and caspase 9 levels, as well as the immunoreactivity of Cleaved caspase 3, were determined in the hippocampus. The results showed that pretreatment with 20 mg/kg SA delayed the latency of generalized tonic-clonic seizures (GTCS) and first myoclonic jerk, reduced GTCS duration, and improved seizure score and cognitive function. Importantly, the 20 mg/kg SA pretreatment resulted in decreased levels of TOS, TNF-α, IL-1β, and BDNF in the cortex and hippocampus, while increasing TAS levels in these brain areas. Moreover, the 20 mg/kg SA reduced hippocampal caspase 3 and caspase 9 levels, as well as the immunoreactivity of Cleaved caspase 3 in rats with pentylenetetrazol-induced seizures. These findings suggest that the anti-seizure effects of SA are mediated by BDNF modulation, as well as its anti-oxidant, anti-inflammatory, and antiapoptotic properties. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the onset of symptoms, typically occurring later in life, and significant deficits in cognitive functions including learning, memory, speech, and behavior. Ongoing research endeavors seek to explore methods for preventing and treating AD, as well as delving into the molecular mechanisms underlying existing and novel therapeutic approaches encompassing exercise, diet, and drug regimens for individuals with AD or those at risk of developing AD. Among these interventions, dietary interventions have garnered increasing attention due to their potential in addressing the disease. Eating is among the most fundamental of human daily activities, and controlled dietary practices, such as fasting, have gained prominence as essential clinical methods for disease prevention and treatment. Research findings indicate that fasting holds promise in effectively alleviating and improving the cognitive decline associated with age or as consequence of disease. The clinical efficacy of fasting in addressing AD and related disorders might be grounded in its influence on various molecular mechanisms, including neuroinflammation, glial cell activation, insulin resistance, autophagy regulation, nerve regeneration, the gut microbiome, and accumulations of amyloid-ß and tau proteins. The present study reviews possible molecular mechanisms underpinning the therapeutic effects of fasting in patients with AD, as well as in models of the disorder, to establish a theoretical basis for using fasting as a viable approach to treat AD. [ABSTRACT FROM AUTHOR]

This study investigates the combined effects of the neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31-Pro34]NPY at a dose of 132 µg and Ketamine at 10 mg/Kg on cognitive functions and neuronal proliferation, against a backdrop where neurodegenerative diseases present an escalating challenge to global health systems. Utilizing male Sprague-Dawley rats in a physiological model, this research employed a single-dose administration of these compounds and assessed their impact 24 h after treatment on object-in-place memory tasks, alongside cellular proliferation within the dorsal hippocampus dentate gyrus. Methods such as the in situ proximity ligation assay and immunohistochemistry for proliferating a cell nuclear antigen (PCNA) and doublecortin (DCX) were utilized. The results demonstrated that co-administration significantly enhanced memory consolidation and increased neuronal proliferation, specifically neuroblasts, without affecting quiescent neural progenitors and astrocytes. These effects were mediated by the potential formation of NPY1R-TrkB heteroreceptor complexes, as suggested by receptor co-localization studies, although further investigation is required to conclusively prove this interaction. The findings also highlighted the pivotal role of brain-derived neurotrophic factor (BDNF) in mediating these effects. In conclusion, this study presents a promising avenue for enhancing cognitive functions and neuronal proliferation through the synergistic action of the NPY1R agonist and Ketamine, potentially via NPY1R-TrkB heteroreceptor complex formation, offering new insights into therapeutic strategies for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Here, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7‐day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin‐1, LC3, p62 and cleaved caspase‐3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin‐1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase‐3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin‐1, LC3 and p62 and inhibiting the apoptotic caspase‐3 protein while its beneficial effects were apparent in neurological tests from the 4th day. [ABSTRACT FROM AUTHOR]

The PTEN gene negatively regulates the oncogenic PI3K-AKT pathway by encoding a lipid and protein phosphatase that dephosphorylates lipid phosphatidylinositol-3,4,5-triphosphate (PIP3) resulting in the inhibition of PI3K and downstream inhibition of AKT. Overexpression of PTEN in mice leads to a longer lifespan compared to control littermates, although the mechanism is unknown. Here, we provide evidence that young adult PTENOE mice exhibit many characteristics shared by other slow-aging mouse models, including those with mutations that affect GH/IGF1 pathways, calorie-restricted mice, and mice treated with anti-aging drugs. PTENOE white adipose tissue (WAT) has increased UCP1, a protein linked to increased thermogenesis. WAT of PTENOE mice also shows a change in polarization of fat-associated macrophages, with elevated levels of arginase 1 (Arg1, characteristic of M2 macrophages) and decreased production of inducible nitric oxide synthase (iNOS, characteristic of M1 macrophages). Muscle and hippocampus showed increased expression of the myokine FNDC5, and higher levels of its cleavage product irisin in plasma, which has been linked to increased conversion of WAT to more thermogenic beige/brown adipose tissue. PTENOE mice also have an increase, in plasma and liver, of GPLD1, which is known to improve cognition in mice. Hippocampus of the PTENOE mice has elevation of both BDNF and DCX, indices of brain resilience and neurogenesis. These changes in fat, macrophages, liver, muscle, hippocampus, and plasma may be considered "aging rate indicators" in that they seem to be consistently changed across many of the long-lived mouse models and may help to extend lifespan by delaying many forms of late-life illness. Our new findings show that PTENOE mice can be added to the group of long-lived mice that share this multi-tissue suite of biochemical characteristics. [ABSTRACT FROM AUTHOR]

Historically, progesterone has been studied significantly within the context of reproductive biology. However, there is now an abundance of evidence for its role in regions of the central nervous system (CNS) associated with such nonreproductive functions that include cognition and affect. Here, we describe mechanisms of progesterone action that support its brain-protective effects, and focus particularly on the role of neurotrophins (such as brain-derived neurotrophic factor, BDNF), the receptors that are critical for their regulation, and the role of certain microRNA in influencing the brain-protective effects of progesterone. In addition, we describe evidence to support the particular importance of glia in mediating the neuroprotective effects of progesterone. Through this review of these mechanisms and our own prior published work, we offer insight into why the effects of a progestin on brain protection may be dependent on the type of progestin (e.g., progesterone versus the synthetic, medroxyprogesterone acetate) used, and age, and as such, we offer insight into the future clinical implication of progesterone treatment for such disorders that include Alzheimer's disease, stroke, and traumatic brain injury. [ABSTRACT FROM AUTHOR]

Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55–90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This single-center study aimed to explore the relationship between lipid profiles and BDNF levels in 90 patients who had experienced AIS for the first time. The results show that the high BDNF group (≥3.227 ng/mL) had significantly higher HbA1C and TG levels; ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C; and percentage of hyperlipidemia (60%) as well as lower levels of HDL-C, with an OR of 1.903 (95% CI: 1.187–3.051) for TG/HDL-C, 1.975 (95% CI: 1.188–3.284) for TC/HDL-C, and 2.032 (95% CI: 1.113–3.711) for LDL-C/HDL-C. Plasma BDNF levels were found to be significantly positively correlated with TG and negatively with HDL-C, with OR values of 1.017 (95% CI: 1.003–1.030) and 0.926 (95% CI: 0.876–0.978), respectively. TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C ratios are associated with BDNF levels in AIS patients. The results also indicate that, in AIS patients, higher BDNF levels are associated with lower HDL and higher TG concentrations. [ABSTRACT FROM AUTHOR]

In female mammals, the proliferation and apoptosis of granulosa cells (GCs) are critical in determining the fate of follicles and are influenced by various factors, including brain-derived neurotrophic factor (BDNF). Previous research has shown that BDNF primarily regulates GC proliferation through the PI3K/AKT, NF-kB, and CREB tumour pathways; however, the role of other molecular mechanisms in mediating BDNF-induced GC proliferation remains unclear. In this study, we investigated the involvement of the m6A reader YTH domain-containing family member 2 (YTHDF2) in BDNF-stimulated GC proliferation and its underlying mechanism. GCs were cultured in DMEM medium supplemented with varying BDNF concentrations (0, 10, 30, 75, and 150 ng/mL) for 24 h. The viability, number, and cell cycle of GCs were assessed using the CCK-8 assay, cell counting, and flow cytometry, respectively. Further exploration into YTHDF2's role in BDNF-stimulated GC proliferation was conducted using RT-qPCR, Western blotting, and sequencing. Our findings indicate that YTHDF2 mediates the effect of BDNF on GC proliferation. Additionally, this study suggests for the first time that BDNF promotes YTHDF2 expression by increasing the phosphorylation level of the ERK1/2 signalling pathway. This study offers a new perspective and foundation for further elucidating the mechanism by which BDNF regulates GC proliferation. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a neurodegenerative disease that causes physical damage to neuronal connections, leading to brain atrophy. This disruption of synaptic connections results in mild to severe cognitive impairments. Unfortunately, no effective treatment is currently known to prevent or reverse the symptoms of AD. The aim of this study was to investigate the effects of three synthetic peptides, i.e., KLVFF, RGKLVFFGR and RIIGL, on an AD in vitro model represented by differentiated SH-SY5Y neuroblastoma cells exposed to retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). The results demonstrated that RIIGL peptide had the least significant cytotoxic activity to normal SH-SY5Y while exerting high cytotoxicity against the differentiated cells. The mechanism of RIIGL peptide in the differentiated SH-SY5Y was investigated based on changes in secretory proteins compared to another two peptides. A total of 380 proteins were identified, and five of them were significantly detected after treatment with RIIGL peptide. These secretory proteins were found to be related to microtubule-associated protein tau (MAPT) and amyloid-beta precursor protein (APP). RIIGL peptide acts on differentiated SH-SY5Y by regulating amyloid-beta formation, neuron apoptotic process, ceramide catabolic process, and oxidative phosphorylation and thus has the potentials to treat AD.

Background: Impulsivity assessment may serve as a valuable clinical tool in the stratification of suicide risk. Acting without forethought is a crucial feature in the psychopathology of many psychiatric disturbances and corresponds with suicidal ideations, behaviors, and attempts. Methods: We present data on biological and psychological correlates of impulsivity among young adults (n = 47). Psychological analysis included both the self-description questionnaire—Barratt Impulsiveness Scale (BIS-11)—and neuropsychological behavioral tests, including the Iowa Gambling Task (IGT), the Simple Response Time task (SRT), and the Continuous Performance Test (CPT). mRNA and micro-RNA were isolated from peripheral blood mononuclear cells (PBMC). Expression levels of Brain-Derived Neurotrophic Factor (BDNF) mRNA and its regulatory micro RNAs, mir-1-3p, mir-15a-5p, mir-26a-5p, mir-26b-5p, and mir-195-5p, were analyzed using the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. proBDNF and BDNF plasma protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). Results: Significant correlations between BDNF mRNA and mir-15a-5p as well as proBDNF levels and mir-1-3p were detected. proBDNF protein levels correlated with motor and perseverance, while mir-26b correlated with cognitive complexity subdimensions of the BIS-11 scale. Correlations between BDNF, miRNAs, and the results of neuropsychological tests were also detected. Conclusions: The BDNF pathway shows a clinical potential in searching for biomarkers of impulse-control impairment. BDNF-regulatory micro-RNAs are detectable and related to clinical parameters in the studied population, which needs further research.

Abstract Background Alzheimer’s disease (AD) is an age-related disease characterized by altered cognition, neuroinflammation, and neurodegeneration against which there is presently no effective cure. Brain-derived neurotrophic factor (BDNF) is a key neurotrophin involved in the learning and memory process, with a crucial role in synaptic plasticity and neuronal survival. Several findings support that a reduced BDNF expression in the human brain is associated with AD pathogenesis. BDNF has been proposed as a potential therapy for AD, but BDNF has low brain penetration. In this study, we used an innovative encapsulated cell biodelivery (ECB) device, containing genetically modified cells capable of releasing BDNF and characterized its feasibility and therapeutic effects in the novel App knock-in AD mouse model (App NL−G−F ). Methods ECB’s containing human ARPE-19 cells genetically modified to release BDNF (ECB-BDNF devices) were stereotactically implanted bilaterally into hippocampus of 3-month-old App NL−G−F mice. The stability of BDNF release and its effect on AD pathology were evaluated after 1, 2-, and 4-months post-implantation by immunohistochemical and biochemical analyses. Exploratory and memory performance using elevated plus maze (EPM) and Y-maze test were performed in the 4-months treatment group. Immunological reaction towards ECB-BDNF devices were studied under ex vivo and in vivo settings. Results The surgery and the ECB-BDNF implants were well tolerated without any signs of unwanted side effects or weight loss. ECB-BDNF devices did not induce host-mediated immune response under ex vivo set-up but showed reduced immune cell attachment when explanted 4-months post-implantation. Elevated BDNF staining around ECB-BDNF device proximity was detected after 1, 2, and 4 months treatment, but the retrieved devices showed variable BDNF release. A reduction of amyloid-β (Aβ) plaque deposition was observed around ECB-BDNF device proximity after 2-months of BDNF delivery. Conclusions The result of this study supports the use of ECB device as a promising drug-delivery approach to locally administer BBB-impermeable factors for treating neurodegenerative conditions like AD. Optimization of the mouse-sized devices to reduce variability of BDNF release is needed to employ the ECB platform in future pre-clinical research and therapy development studies.

The consequence of appropriate food consumption and the corresponding amount of dietary nutrients on brain function is widely recognized. More and more studies are pointing to the importance of diet for alleviating neurological symptoms associated with a wide range of clinical disorders. The recently discovered implications of nutritional variables on modifications in mitochondrial dysfunction, epigenetic modification, and neurological inflammation represent important factors that play a crucial role in determining the effect of nutrition on Neuronal (health). This overview investigates the present state of evidence regarding the efficacy of various dietary interventions, such as dietary supplements and dietary restrictions, for in the context of managing disorders related to the brain. Particularly, it clearly state the consequences of these interventions on conditions such as Alzheimer's, Parkinson's, ischemic stroke, seizures, injury to the brain, amyotrophic lateral sclerosis (ALL), Huntington's syndrome, and multiple sclerosis (MS). Along with this, it is important to note that a variety of possible processes, such as metabolic regulation, epigenetic alteration, and the inflammation of neurons assume a pivotal function. in determining the impact of nutrition availability on the risk of neurologic conditions and treatment outcomes. Along with this, authors clearly state the innovative concept that dietary supplement intervention can modify interconnected processes of metabolism, epigenetics, and immunology, thereby addressing brain dysfunction. Concentrating on metabolic processes the study of the epigenetic-immunity network has the potential to provide a novel framework for addressing vulnerabilities in the field of neurology.

Historically, progesterone has been studied significantly within the context of reproductive biology. However, there is now an abundance of evidence for its role in regions of the central nervous system (CNS) associated with such non-reproductive functions that include cognition and affect. Here, we describe mechanisms of progesterone action that support its brain-protective effects, and focus particularly on the role of neurotrophins (such as brain-derived neurotrophic factor, BDNF), the receptors that are critical for their regulation, and the role of certain microRNA in influencing the brain-protective effects of progesterone. In addition, we describe evidence to support the particular importance of glia in mediating the neuroprotective effects of progesterone. Through this review of these mechanisms and our own prior published work, we offer insight into why the effects of a progestin on brain protection may be dependent on the type of progestin (e.g., progesterone versus the synthetic, medroxyprogesterone acetate) used, and age, and as such, we offer insight into the future clinical implication of progesterone treatment for such disorders that include Alzheimer’s disease, stroke, and traumatic brain injury.

Background: The aim of this pilot randomized controlled trial was to test the feasibility of a computerized cognitive training targeting executive dysfunction in late-life depression and to investigate its impact on mood, cognition, and brain-derived neurotrophic factor (BDNF) levels. Methods: A total of 28 community-living Chinese individuals aged 55–75 with moderate-to-severe depression and cognitive symptoms (but without mild cognitive impairment or dementia) were recruited from a community centre in Hong Kong. Participants were randomly allocated to either the experimental (receiving computerized cognitive training) or the control group (receiving computer-based health education). Both programs lasted for one hour and were conducted twice a week for 6  weeks at the community centre. We assessed mood using the Hamilton Rating Scale for Depression (HAM-D) and Patient Health Questionaire-9 (PHQ-9), cognition using the Montreal Cognitive Assessment (MoCA), and serum BDNF levels at baseline and followup. We performed repeated measures analysis of variance to compare the differences in outcome changes between groups and correlation analysis to test if changes in mood and cognition correlated with changes in BDNF level. Results: Our sample had a mean age of 66.8 (SD  =  5.3) years, a mean HAM-D score of 19.4 (SD  =  7.5), and a mean PHQ-9 score of 18.0 (SD  =  6.3). No adverse effects were reported. Significant differences were observed between the experimental and control groups in changes in HAM-D (-8.4 vs. -2.9; group difference  = -5.5; p  =  0.01), PHQ-9 (-6.6 vs. -0.6; -6.0; p  <  0.001), MoCA (1.4 vs. -1.3; 2.7; p  =  0.001), and serum BDNF levels (in pg/ml; 2088.3 vs. -3277.4; 5365.6; p  =  0.02). Additionally, changes in HAM-D, PHQ-9, and MoCA scores correlated significantly with changes in BDNF level. Conclusion: With computerized cognitive training improving mood and cognition and increasing serum BDNF levels in 6  weeks, it may serve as a safe and effective evidence-based alternative or adjuvant treatment for late-life depression. [ABSTRACT FROM AUTHOR]

The role of neurotrophic factors, oxidative stress, and inflammation in the pathogenesis of Alzheimer's disease (AD) has been explored. Animal studies have reported the positive effects of probiotics on these factors. Some clinical studies also support the potential role of probiotics in improving cognitive function via the gut–brain axis in older adults. However, clinical experimental studies evaluating the efficacy of probiotics targeting the neurotrophic factors and inflammatory biomarkers, particularly among AD patients, remain very limited. In this randomized, double-blinded, active-controlled trial, we used multi-strain probiotic supplements, including Bifidobacterium longum subsp. infantis BLI-02, B. breve Bv-889, B. animalis subsp. lactis CP-9, B. bifidum VDD088, and Lactobacillus plantarum PL-02 as the intervention. Participants were divided into an active control group (received probiotic supplements containing 5 × 107 colony-forming units per day, CFU/day) and a treatment group (1 × 1010 CFU/day). Student's t test was applied as the main method of statistical analysis. After 12 weeks of intervention, the treatment group demonstrated a 36% increase in serum brain-derived neurotrophic factor (BDNF) (* p = 0.005), a reduction in IL-1β (* p = 0.041), and an increase in antioxidant superoxide dismutase (SOD) (* p = 0.012). No significant change was found in the active control group. A trend toward less cognitive deterioration was observed, but not statistically significant. In conclusion, this study presents evidence supporting the benefits of multi-strain probiotics in enhancing BDNF, ameliorating inflammation and oxidative stress in AD patients. [ABSTRACT FROM AUTHOR]

Introduction: Zuotai is an ancient mineral-herbal mixture containing β-HgS in Tibetan medicine. It is used to treat nervous system diseases, similar to Chinese medicine cinnabar and Indian Ayurveda medicine Rasasindura. However, one of the key problems faced by Zuotai is that its indications are ambiguous. Our previous study found that Zuotai exhibited the activity of ameliorating depressive-like behaviors in a chronic mild stress model. However, due to the inherent limitations of animal models in simulating human disease, clear results often require more than one model for confirmation. Methods: Therefore, another depression model, chronic restraint stressed (CRS) mice, was used to validate the antidepression effect of Zuotai. Prophylactic treatment was conducted for 21 consecutive days while mice were subjected to chronic restraint stress. Results: It was observed that Zuotai and β-HgS alleviated anhedonia, behavioral despair, stereotype behavior, and reduced exploratory and spontaneous movement in CRS mice. Zuotai and β-HgS also reversed the increases of stress hormone corticosterone (Cort) in serum and pro-inflammatory cytokines in serum and brain, and increased the serotonin in cortex in CRS mice, with positive dose-effect relationship. The number of Ki67-positive cells in the dentate gyrus and the level of brain-derived neurotrophic factor (BDNF) in the hippocampus were slightly elevated in CRS mice treated with Zuotai; however, there was no statistically significant difference. Although Zuotai increased the total Hg concentration in main organs, the levels remained below those needed to result in observed adverse effect, at least for kidney and liver; and Zuotai showed no observed adverse effect on the brain histopathology, the cell proliferation in dentate gyrus, as well as the hippocampal and cortical organ coefficients. Conclusion: Zuotai exhibited the alleviation of depressive-like behaviors in CRS mice, accompanying with ameliorating stress hormone, peripherical and cerebral inflammation, and monoamine neurotransmitter. [ABSTRACT FROM AUTHOR]

Over the last decade, a considerable amount of new data have revealed the beneficial effects of exercise on hippocampal neurogenesis and the maintenance or improvement of cognitive function. Investigations with animal models, as well as human studies, have yielded novel understanding of the mechanisms through which endocrine signaling can stimulate neurogenesis, as well as the effects of exercise on acute and/or chronic levels of these circulating hormones. Considering the effects of aging on the decline of specific endocrine factors that affect brain health, insights in this area of research are particularly important. In this review, we discuss how different forms of exercise influence the peripheral production of specific endocrine factors, with particular emphasis on brainderived neurotrophic factor, growth hormone, insulin-like growth factor-1, ghrelin, estrogen, testosterone, irisin, vascular endothelial growth factor, erythropoietin, and cortisol. We also describe mechanisms through which these endocrine responses to exercise induce cellular changes that increase hippocampal neurogenesis and improve cognitive function. [ABSTRACT FROM AUTHOR]

Nonsuicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD and suicidal ideation. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD and suicidal ideation was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, neuronal survival, plasticity, and excitability, all of which are disrupted in neurological and cognitive disorders such as Alzheimer's disease (AD). Extracellular aggregates of amyloid-β (Aβ) in the form of plaques and intracellular aggregates of hyperphosphorylated tau protein have been identified as major pathological insults in the AD brain, along with immune dysfunction, oxidative stress, and other toxic stressors. Although aggregated Aβ and tau lead to decreased brain BDNF expression, early losses in BDNF prior to plaque and tangle formation may be due to other insults such as oxidative stress and contribute to early synaptic dysfunction. Physical exercise, on the other hand, protects synaptic and neuronal structure and function, with increased BDNF as a major mediator of exercise-induced enhancements in cognitive function. Here, we review recent literature on the mechanisms behind exercise-induced BDNF upregulation and its effects on improving learning and memory and on Alzheimer's disease pathology. Exercise releases into the circulation a host of hormones and factors from a variety of peripheral tissues. Mechanisms of BDNF induction discussed here are osteocalcin, FNDC5/irisin, and lactate. The fundamental mechanisms of how exercise impacts BDNF and cognition are not yet fully understood but are a prerequisite to developing new biomarkers and therapies to delay or prevent cognitive decline. [ABSTRACT FROM AUTHOR]

Over the last decade, a considerable amount of new data have revealed the beneficial effects of exercise on hippocampal neurogenesis and the maintenance or improvement of cognitive function. Investigations with animal models, as well as human studies, have yielded novel understanding of the mechanisms through which endocrine signaling can stimulate neurogenesis, as well as the effects of exercise on acute and/or chronic levels of these circulating hormones. Considering the effects of aging on the decline of specific endocrine factors that affect brain health, insights in this area of research are particularly important. In this review, we discuss how different forms of exercise influence the peripheral production of specific endocrine factors, with particular emphasis on brain-derived neurotrophic factor, growth hormone, insulin-like growth factor-1, ghrelin, estrogen, testosterone, irisin, vascular endothelial growth factor, erythropoietin, and cortisol. We also describe mechanisms through which these endocrine responses to exercise induce cellular changes that increase hippocampal neurogenesis and improve cognitive function.

Stroke is one of the leading causes of death and the primary source of disability in adults, resulting in neuronal necrosis of ischemic areas, and in possible secondary degeneration of regions surrounding or distant to the initial damaged area. Secondary neurodegeneration (SNDG) following stroke has been shown to have different pathogenetic origins including inflammation, neurovascular response and cytotoxicity, but can be associated also to regenerative processes. Aside from focal neuronal loss, ipsilateral and contralateral effects distal to the lesion site, disruptions of global functional connectivity and a transcallosal diaschisis have been reported in the chronic stages after stroke. Furthermore, SNDG can be observed in different areas not directly connected to the primary lesion, such as thalamus, hippocampus, amygdala, substantia nigra, corpus callosum, bilateral inferior fronto-occipital fasciculus and superior longitudinal fasciculus, which can be highlighted by neuroimaging techniques. Although the clinical relevance of SNDG following stroke has not been well understood, the identification of specific biomarkers that reflect the brain response to the damage, is of paramount importance to investigate in vivo the different phases of stroke. Actually, brain-derived markers, particularly neurofilament light chain, tau protein, S100b, in post-stroke patients have yielded promising results. This review focuses on cerebral morphological modifications occurring after a stroke, on associated cellular and molecular changes and on state-of-the-art of biomarkers in acute and chronic phase. Finally, we discuss new perspectives regarding the implementation of blood-based biomarkers in clinical practice to improve the rehabilitation approaches and post stroke recovery. [ABSTRACT FROM AUTHOR]

The adsorption of biomolecules on nanoparticles' surface ultimately depends on the intermolecular forces, which dictate the mutual interaction transforming their physical, chemical, and biological characteristics. Therefore, a better understanding of the adsorption of serum proteins and their impact on nanoparticle physicochemical properties is of utmost importance for developing nanoparticle-based therapies. We investigated the interactions between potentially therapeutic proteins, neurotrophin 3 (NT3), brain-derived neurotrophic factor (BDNF), and polyethylene glycol (PEG), in a cell-free system and a retinal pigmented epithelium cell line (ARPE-19). The variance in the physicochemical properties of PEGylated NT3–BDNF nanoparticles (NPs) in serum-abundant and serum-free systems was studied using transmission electron microscopy, atomic force microscopy, multi-angle dynamic, and electrophoretic light scattering. Next, we compared the cellular response of ARPE-19 cells after exposure to PEGylated NT3–BDNF NPs in either a serum-free or complex serum environment by investigating protein release and cell cytotoxicity using ultracentrifuge, fluorescence spectroscopy, and confocal microscopy. After serum exposure, the decrease in the aggregation of PEGylated NT3–BDNF NPs was accompanied by increased cell viability and BDNF/NT3 in vitro release. In contrast, in a serum-free environment, the appearance of positively charged NPs with hydrodynamic diameters up to 900 nm correlated with higher cytotoxicity and limited BDNF/NT3 release into the cell culture media. This work provides new insights into the role of protein corona when considering the PEGylated nano–bio interface with implications for cytotoxicity, NPs' distribution, and BDNF and NT3 release profiles in the in vitro setting. [ABSTRACT FROM AUTHOR]

The main aim of this systematic review and meta-analysis is to establish whether there is a correlation between the brain-derived neurotrophic factor (BDNF) level and electroconvulsive therapy (ECT) treatment and the reduction in psychotic symptoms in patients diagnosed with schizophrenia. A systematic search of PubMed/Medline, Cochrane Library, Web of Science, Scopus and Embase was conducted up to March 2023. Inclusion criteria: studies in which adult patients with schizophrenia treated with antipsychotic medication received ECT therapy and had the BDNF level measured before and after ECT treatment. Exclusion criteria: animal and in vitro studies or studies not involving complete information about the treatment and concentration of BDNF in plasma. The risk of bias was assessed using Egger's regression-based test for meta-analysis with continuous outcomes. Six studies comprising 248 individuals with schizophrenia were included. A statistically significant increase in BDNF levels after ECT treatment was observed only in two studies (p < 0.001 and p < 0.027, respectively), whereas in four other studies, an upward trend without statistical significance was noticed. The estimated overall size effect revealed that ECT therapy caused a slight change in the BDNF level but without statistical significance (ES = −0.328). Different numbers of ECT procedures (4-10), final measurement of the BDNF level made at a different time point, using bilateral or unilateral electrode positioning during ECT and treatment with different combinations of typical or atypical antipsychotic medications may be potential reasons for the lack of statistical significance in the changes in BDNF levels after treatment. Data regarding the measurement of BDNF levels pre and post ECT therapy in patients with schizophrenia are very limited without an extended follow-up period and evaluation of mental health change. Our meta-analysis showed that treatment with ECT therapy and antipsychotic medication increases serum BDNF levels in patients with drug-resistant schizophrenia compared to patients treated with medication only; however, this effect is not statistically significant. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is an age-related disease characterized by altered cognition, neuroinflammation, and neurodegeneration against which there is presently no effective cure. Brain-derived neurotrophic factor (BDNF) is a key neurotrophin involved in the learning and memory process, with a crucial role in synaptic plasticity and neuronal survival. Several findings support that a reduced BDNF expression in the human brain is associated with AD pathogenesis. BDNF has been proposed as a potential therapy for AD, but BDNF has low brain penetration. In this study, we used an innovative encapsulated cell biodelivery (ECB) device, containing genetically modified cells capable of releasing BDNF and characterized its feasibility and therapeutic effects in the novel App knock-in AD mouse model (AppNL−G−F). Methods: ECB's containing human ARPE-19 cells genetically modified to release BDNF (ECB-BDNF devices) were stereotactically implanted bilaterally into hippocampus of 3-month-old AppNL−G−F mice. The stability of BDNF release and its effect on AD pathology were evaluated after 1, 2-, and 4-months post-implantation by immunohistochemical and biochemical analyses. Exploratory and memory performance using elevated plus maze (EPM) and Y-maze test were performed in the 4-months treatment group. Immunological reaction towards ECB-BDNF devices were studied under ex vivo and in vivo settings. Results: The surgery and the ECB-BDNF implants were well tolerated without any signs of unwanted side effects or weight loss. ECB-BDNF devices did not induce host-mediated immune response under ex vivo set-up but showed reduced immune cell attachment when explanted 4-months post-implantation. Elevated BDNF staining around ECB-BDNF device proximity was detected after 1, 2, and 4 months treatment, but the retrieved devices showed variable BDNF release. A reduction of amyloid-β (Aβ) plaque deposition was observed around ECB-BDNF device proximity after 2-months of BDNF delivery. Conclusions: The result of this study supports the use of ECB device as a promising drug-delivery approach to locally administer BBB-impermeable factors for treating neurodegenerative conditions like AD. Optimization of the mouse-sized devices to reduce variability of BDNF release is needed to employ the ECB platform in future pre-clinical research and therapy development studies. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most frequent worldwide cause of adult population disabilities. The study evaluated the effects of a 21-day individual rehabilitation exercise training program focused on improving patients' functional capacity. The study analyzed the changes in irisin, chemerin, and BDNF serum levels in 36 OA patients subjected to an individually-adjusted rehabilitation program 90 days after surgical hip or knee replacement. The changes in irisin, chemerin, and BDNF serum levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. A 21-day individual rehabilitation exercise training program significantly increased irisin and BDNF, and decreased chemerin serum levels. The presented study indicates that individually-adjusted exercise training is an important modulator influencing serum levels of anti- and pro-inflammatory factors, leading to positive clinical outcomes in osteoarthritis therapy. Selected factors are considered potential markers of various pathophysiological conditions. The presented study brings new details to the discussion. [ABSTRACT FROM AUTHOR]

Average and maximal lifespan can be increased in mice, in one or both sexes, by four drugs: rapamycin, acarbose, 17a-estradiol, and canagliflozin. We show here that these four drugs, as well as a calorie-restricted diet, can induce a common set of changes in fat, macrophages, plasma, muscle, and brain when evaluated in young adults at 12 months of age. These shared traits include an increase in uncoupling protein UCP1 in brown fat and in subcutaneous and intra-abdominal white fat, a decline in proinflammatory M1 macrophages and corresponding increase in anti-inflammatory M2 macrophages, an increase in muscle fibronectin type III domain containing 5 (FNDC5) and its cleavage product irisin, and higher levels of doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) in brain. Each of these proteins is thought to play a role in one or more age-related diseases, including metabolic, inflammatory, and neurodegenerative diseases. We have previously shown that the same suite of changes is seen in each of four varieties of slow-aging single-gene mutant mice. We propose that these changes may be a part of a shared common pathway that is seen in slow-aging mice whether the delayed aging is due to a mutation, a low-calorie diet, or a drug. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) interacts with tropomyosin-related kinase B (TrkB) to promote neuronal growth, survival, differentiation, neurotransmitter release, and synaptic plasticity. The translocator protein (TSPO) is known to be found in arterial plaques, which are a symptom of atherosclerosis and a contributory cause of ischemic stroke. This study aims to determine the diagnostic accuracy of plasma BDNF and TSPO levels in discriminating new-onset acute ischemic stroke (AIS) patients from individuals without acute ischemic stroke. A total of 90 AIS patients (61% male, with a mean age of 67.7 ± 12.88) were recruited consecutively in a stroke unit, and each patient was paired with two age- and gender-matched controls. The sensitivity, specificity, and area of the curve between high plasma BDNF and TSPO and having AIS was determined using receiver operating characteristic curves. Furthermore, compared to the controls, AIS patients exhibited significantly higher levels of BDNF and TSPO, blood pressure, HbA1c, and white blood cells, as well as higher creatinine levels. The plasma levels of BDNF and TSPO can significantly discriminate AIS patients from healthy individuals (AUC 0.76 and 0.89, respectively). However, combining the two biomarkers provided little improvement in AUC (0.90). It may be possible to use elevated levels of TSPO as a diagnostic biomarker in patients with acute ischemic stroke upon admission. [ABSTRACT FROM AUTHOR]

Simple Summary: The ever-increasing number of CRC cases and the associated number of deaths from this type of cancer require the development of sensitive, accurate, and non-invasive biomarkers for the early detection of CRC. At the same time, it is necessary to characterize these biomarkers in relation to the individual stages of CRC. We achieved interesting results by creating a BDNF/MMP9 ratio. The tissue BDNF/MMP-9 ratio (evaluated immunohistochemically) decreased significantly with the progression of the disease in living patients. However, in deceased individuals, the ratio showed an opposite tendency. We can conclude that lower BNDF/MMP-9 ratio levels may predict patients with a favorable prognosis. Our results confirmed the existence of a direct connection between the pro-plastic molecules BDNF and MMP-9. Purpose: The development of sensitive and non-invasive biomarkers for the early detection of CRC and determination of their role in the individual stages of CRC. Methods: MMP-9 expression in serum and tissue, and BDNF expression in plasma were detected using the ELISA method. MMP-9 and BDNF in the tissue were also determined by immunohistochemical staining. Results: To assess the balance between changes in survival and tumor progression, we compared BDNF/MMP-9 ratios in tissues of living and deceased individuals. The tissue BDNF/MMP-9 ratio (evaluated immunohistochemically) decreased significantly with the progression of the disease in living patients. The BDNF/MMP-9 ratio was statistically significantly reduced in stages II and III compared to the benign group. However, in deceased individuals, the ratio showed an opposite tendency. Conclusion: The determination of the tissue BDNF/MMP9 ratio can be used as a prognostic biomarker of CRC. [ABSTRACT FROM AUTHOR]

The immediate early gene product activity-regulated cytoskeleton-associated protein (Arc or Arg3.1) is a major regulator of long-term synaptic plasticity with critical roles in postnatal cortical development and memory formation. However, the molecular basis of Arc function is undefined. Arc is a hub protein with interaction partners in the postsynaptic neuronal compartment and nucleus. Previous in vitro biochemical and biophysical analysis of purified recombinant Arc showed formation of low-order oligomers and larger particles including retrovirus-like capsids. Here, we provide evidence for naturally occurring Arc oligomers in the mammalian brain. Using in situ protein crosslinking to trap weak Arc-Arc interactions, we identified in various preparations a prominent Arc immunoreactive band on SDS-PAGE of molecular mass corresponding to a dimer. While putative trimers, tetramers and heavier Arc species were detected, they were of lower abundance. Stimulus-evoked induction of Arc expression and dimer formation was first demonstrated in SH-SY5Y neuroblastoma cells treated with the muscarinic cholinergic agonist, carbachol, and in primary cortical neuronal cultures treated with brain-derived neurotrophic factor (BDNF). In the dentate gyrus (DG) of adult anesthetized rats, induction of long-term potentiation (LTP) by high-frequency stimulation (HFS) of medial perforant synapses or by brief intrahippocampal infusion of BDNF led to a massive increase in Arc dimer expression. Arc immunoprecipitation of crosslinked DG tissue showed enhanced dimer expression during 4 h of LTP maintenance. Mass spectrometric proteomic analysis of immunoprecipitated, gel-excised bands corroborated detection of Arc dimer. Furthermore, Arc dimer was constitutively expressed in naïve cortical, hippocampal and DG tissue, with the lowest levels in the DG. Taken together the results implicate Arc dimer as the predominant low-oligomeric form in mammalian brain, exhibiting regional differences in its constitutive expression and enhanced synaptic activity-evoked expression in LTP. [ABSTRACT FROM AUTHOR]

Background and purpose: Intracerebral hemorrhage (ICH) enhances neurogenesis in the subventricular zone (SVZ); however, the mechanism is not fully understood. We investigated the role of brain-derived neurotrophic factor (BDNF) in post-ICH neurogenesis in a rodent model and in patients with ICH using cerebrospinal fluid (CSF). Methods: A rat model of ICH was constructed via stereotaxic injection of collagenase into the left striatum. Patients with ICH receiving an external ventricular drain were prospectively enrolled. CSF was collected from rats and patients at different post-ICH times. Primary cultured rat neural stem cells (NSCs) were treated with CSF with or without BDNF-neutralized antibody. Immunohistochemistry and immunocytochemistry were used to detect NSC proliferation and differentiation. The BDNF concentration in CSF was quantified using enzyme-linked immunosorbent assays (ELISA). Results: In the rat model of ICH, the percentage of proliferating NSCs and neuroblasts in SVZ was elevated in bilateral hemispheres. The cultured rat NSCs treated with CSF from both rats and patients showed an increased capacity for proliferation and differentiation toward neuroblasts. BDNF concentration was higher in CSF collected from rats and patients with ICH than in controls. Blocking BDNF decreased the above-noted promotion of proliferation and differentiation of cultured NSCs by CSF treatment. In patients with ICH, the BDNF concentration in CSF and the neurogenesis-promoting capacity of post-ICH CSF correlated positively with ICH volume. Conclusion: BDNF in CSF contributes to post-ICH neurogenesis, including NSC proliferation and differentiation toward neuroblasts in a rat model and patients with ICH. [ABSTRACT FROM AUTHOR]

Methamphetamine use can induce psychosis resembling acute schizophrenia spectrum psychosis, making it challenging to differentiate between the two based on symptoms alone. Brain-derived neurotrophic factor (BDNF) exerts a critical role in hippocampal neural plasticity, influencing critical cognitive functions such as memory and learning. This study aimed to determine the role of serum BDNF levels in schizophrenia and methamphetamine addiction. A case-control study was conducted involving 50 patients with schizophrenia, 50 patients with methamphetamine addiction, and 50 healthy control subjects recruited from Ibn-Rushed Psychiatric Teaching Hospital in Baghdad. Cognitive impairment was assessed using the Mini-Mental State Examination (MMSE), while serum BDNF levels were measured using ELISA following standardized protocols. The findings revealed significantly lower median levels of BDNF (0.36 pg/ml) in patients with schizophrenia compared to both the control group (0.51 pg/ml) and the methamphetamine group (0.72 pg/ml). Moreover, there was a significant difference observed between the methamphetamine group and the control group. At a cut-off value of BDNF=0.37 pg/ml, the sensitivity and specificity of BDNF in differentiating between schizophrenia and methamphetamine addiction were 84% and 70%, respectively. Serum level of BDNF could be used to differentiate between schizophrenia and methamphetamine addiction when clinical distinctions are challenging to detect. [ABSTRACT FROM AUTHOR]

Stroke is one of the leading causes of death and the primary source of disability in adults, resulting in neuronal necrosis of ischemic areas, and in possible secondary degeneration of regions surrounding or distant to the initial damaged area. Secondary neurodegeneration (SNDG) following stroke has been shown to have different pathogenetic origins including inflammation, neurovascular response and cytotoxicity, but can be associated also to regenerative processes. Aside from focal neuronal loss, ipsilateral and contralateral effects distal to the lesion site, disruptions of global functional connectivity and a transcallosal diaschisis have been reported in the chronic stages after stroke. Furthermore, SNDG can be observed in different areas not directly connected to the primary lesion, such as thalamus, hippocampus, amygdala, substantia nigra, corpus callosum, bilateral inferior fronto-occipital fasciculus and superior longitudinal fasciculus, which can be highlighted by neuroimaging techniques. Although the clinical relevance of SNDG following stroke has not been well understood, the identification of specific biomarkers that reflect the brain response to the damage, is of paramount importance to investigate in vivo the different phases of stroke. Actually, brain-derived markers, particularly neurofilament light chain, tau protein, S100b, in post-stroke patients have yielded promising results. This review focuses on cerebral morphological modifications occurring after a stroke, on associated cellular and molecular changes and on state-of-the-art of biomarkers in acute and chronic phase. Finally, we discuss new perspectives regarding the implementation of blood-based biomarkers in clinical practice to improve the rehabilitation approaches and post stroke recovery.

Thyroid hormones and the hypothalamic-pituitary-thyroid (HPA) axis are responsible for multiple metabolic processes and psychological well-being. Hypothyroidism can induce mood changes, depressive symptoms and even major depressive disorder. This review is focused on the pathophysiology and mechanisms through which the low level of thyroid hormones may affect the brain function, causing the characteristic symptoms of depression. Key pathways of hypothyroid-associated depressive states include: morphological changes in some brain areas (mainly in the hippocampus – a reduction in its volume); a significant reduction of the cerebral blood flow (incl. hippocampus), and lowered levels of neurotrophic factors (e. g. BDNF – brain-derived neurotrophic factor), which are regulated by the thyroid hormones. An adequate and timely thyroid hormone replacement and treatment with conventional antidepressants often can reverse the psychological symptoms.

Abstract To explore the effect of electroacupuncture on spinal cord injury (SCI) involving immune‐related factors and regeneration‐related factors in rats. The model of spinal cord contusion was established by PCI 3000 instrument. Two types of acupuncture points were selected for electroacupuncture treatment on rats. The rats were tested once a week, and the fiber remodeling was detected by magnetic resonance imaging. Transcriptome sequencing was performed on spinal scar samples. Using Python to write code, statistical analysis and bioinformatics analysis of the correlation between transcriptome sequencing data and fiber reconstruction results are carried out. Lastly, the expression of CD4 and brain‐derived neurotrophic factor (BDNF) in spinal cord scar was verified by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR). Electroacupuncture exhibited a positive effect on the recovery of motor function in rats after SCI. Bioinformatics analysis found a direct interaction between CD4 and BDNF. Transcriptome sequencing and PCR results verified that electroacupuncture significantly reduced the expression of CD4, and increased significantly the expression of BDNF, simultaneously corresponding to nerve regeneration in rats with SCI. Our results showed that electroacupuncture intervention in SCI rats improves neural behavior via inhibiting the expression of CD4 and increasing the expression of BDNF.

Background: Ginsenosides and their metabolites have antidepressant-like effects, but the underlying mechanisms remain unclear. We previously identified 14-3-3 ζ as one of the target proteins of 20 (S)-protopanaxadiol (PPD), a fully deglycosylated ginsenoside metabolite. Methods: Corticosterone (CORT) was administered repeatedly to induce the depression model, and PPD was given concurrently. The tail suspension test (TST) and the forced swimming test (FST) were used for behavioral evaluation. All mice were sacrificed. Golgi-cox staining, GSK 3β activity assay, and Western blot analysis were performed. In vitro, the kinetic binding analysis with the Biolayer Interferometry (BLI) was used to determine the molecular interactions. Results: TST and FST both revealed that PPD reversed CORT-induced behavioral deficits. PPD also ameliorated the CORT-induced expression alterations of hippocampal Ser9 phosphorylated glycogen synthase kinase 3β (p-Ser9 GSK 3β), Ser133 phosphorylated cAMP response element-binding protein (p-Ser133 CREB), and brain-derived neurotrophic factor (BDNF). Moreover, PPD attenuated the CORT-induced increase in GSK 3β activity and decrease in dendritic spine density in the hippocampus. In vitro, 14-3-3 ζ protein specifically bound to p-Ser9 GSK 3β polypeptide. PPD promoted the binding and subsequently decreased GSK 3β activity. Conclusion: These findings demonstrated the antidepressant-like effects of PPD on the CORT-induced mouse depression model and indicated a possible target-based mechanism. The combination of PPD with the 14-3-3 ζ protein may promote the binding of 14-3-3 ζ to p-GSK 3β (Ser9) and enhance the inhibition of Ser9 phosphorylation on GSK 3β kinase activity, thereby activating the plasticity-related CREB–BDNF signaling pathway.