Search Results (332)

Background: Response speed refers to an individual’s ability to perceive and react to harmful stimuli, which can vary due to genetics, neural regulation, and environmental factors. Our previous study demonstrated that whey protein hydrolysate was a potential means to enhance cognitive function. Methods: This study used a variety of behavioral methods to evaluate the functional effects of whey protein hydrolysate on improving reaction speed, and revealed its potential mechanisms through proteomics analysis. Results: The results showed that whey protein hydrolysate improved response speed in mice when tested against thermal pain, mechanical strength stimuli, and prepulse inhibition. Proteomic analysis of the hippocampus revealed changes in proteins related to arginine and proline metabolism, as well as neuroactive ligand–receptor interactions. Conclusions: These findings provide new insights into the neuromodulatory effects of whey protein hydrolysate and support its potential role in enhancing response speed and cognitive performance. Full article

Objective: This study aimed to explore the acute neurophysiological effects of a single oral dose of Astragaloside IV (AS-IV) on EEG-measured brain oscillations and cognitive-relevant spectral markers in healthy young adults. Methods: Twenty healthy adults (8 females, 12 males; mean age: $23.4\pm 2.1$) underwent eyes-closed resting-state EEG recordings before and approximately 90 min after oral intake of 150 mg AS-IV. EEG data were collected using a 21-channel 10–20 system and cleaned via Artifact Subspace Reconstruction and Independent Component Analysis. Data quality was confirmed using a signal-to-noise ratio and 1/f spectral slope. Absolute and relative power values, band ratios, and frontal alpha asymmetry were computed. Statistical comparisons were made using paired t-tests or Wilcoxon signed-rank tests. Results: Absolute power decreased in delta, theta, beta, and gamma bands (p < 0.05) but remained stable for alpha. Relative alpha power increased significantly (p = 0.002), with rises in relative beta, theta, and delta and a drop in relative gamma (p = 0.003). Alpha/beta and theta/beta ratios increased, while delta/alpha decreased. Frontal alpha asymmetry was unchanged. Sex differences were examined in all measures that showed significant changes; however, no sex-dependent effects were found. Conclusions: A single AS-IV dose may acutely modulate brain oscillations, supporting its potential neuroactive properties. Larger placebo-controlled trials, including concurrent psychometric assessments, are needed to verify and contextualize these findings. A single AS-IV dose may acutely modulate brain oscillations, supporting its potential neuroactive properties. Full article

The gut–brain axis (GBA) represents a complex bidirectional communication network that links the gut microbiota (GM) and the central nervous system (CNS). Recent research has revealed that neurosteroids (NSs) play crucial roles in modulating neuroinflammatory responses and promoting neuroprotection. Meanwhile, GM alterations have been associated with various neuroinflammatory and neurodegenerative conditions, such as multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis. This review aims to provide a comprehensive overview of the intricate interactions between NS, GM, and neuroinflammation. We discuss how NS and metabolites can influence neuroinflammatory pathways through immune, metabolic, and neuronal mechanisms. Additionally, we explore how GM modulation can impact neurosteroidogenesis, highlighting potential therapeutic strategies that include probiotics, neuroactive metabolites, and targeted interventions. Understanding these interactions may pave the way for innovative treatment approaches for neuroinflammatory and neurodegenerative diseases, promoting a more integrated view of brain health and disease management. Full article

Background: Finasteride, a 5α-reductase inhibitor commonly prescribed for androgenetic alopecia, has been linked to persistent adverse effects after discontinuation, known as post-finasteride syndrome (PFS). Symptoms include neurological, psychiatric, sexual, and gastrointestinal disturbances. Emerging evidence suggests that PFS may involve disruption of sex steroid homeostasis, neuroactive steroid deficiency (notably allopregnanolone, ALLO), and gut–brain axis alterations. Objective: This study aimed to investigate the effects of finasteride withdrawal (FW) in a rat model and evaluate the potential protective effects of ALLO on gut and hypothalamic inflammation. Methods: Adult male Sprague Dawley rats were treated with finasteride for 20 days, followed by one month of drug withdrawal. A subgroup received ALLO treatment during the withdrawal. Histological, molecular, and biochemical analyses were performed on the colon and hypothalamus. Gut microbiota-derived metabolites and markers of neuroinflammation and blood–brain barrier (BBB) integrity were also assessed. Results: At FW, rats exhibited significant colonic inflammation, including a 4.3-fold increase in Mφ1 levels (p < 0.001), a 2.31-fold decrease in butyrate concentration (p < 0.01), and elevated hypothalamic GFAP and Iba-1 protein expression (+360%, p < 0.01 and +100%, p < 0.01, respectively). ALLO treatment rescued these parameters in both the colon and hypothalamus but only partially restored mucosal and BBB structural integrity, as well as the NF-κB/PPARγ pathway. Conclusions: This preclinical study shows that FW causes inflammation in both the gut and hypothalamus in rats. ALLO treatment helped reduce several of these effects. These results suggest ALLO could have a protective role and have potential as a treatment for PFS patients. Full article

Neuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an endogenous NAS epipregnanolone (EpiP) in wild-type mice using behavioral assessment of hypnosis (loss of righting reflex, LORR) and in vivo electrophysiological recordings. Specifically, local field potentials (LFPs) were recorded from the central medial thalamus (CMT) and electroencephalogram (EEG) signals were recorded from the barrel cortex. We found that EpiP-induced LORR exhibited clear sex differences, with females showing increased sensitivity. Spectral power analysis and thalamocortical (TC) and corticocortical (CC) phase synchronization further supported enhanced hypnotic susceptibility in female mice. Our findings reveal characteristic sex-dependent effects of EpiP on the synchronized electrical activity in both thalamus and cortex. These results support renewed exploration of endogenous NAS as clinically relevant anesthetic agents. Full article

Pharmaceuticals such as fluoxetine, paroxetine, sertraline, and mianserin occur in aquatic environments at low yet persistent concentrations due to their incomplete removal in wastewater treatment plants. Although frequently detected, these neuroactive compounds remain underrepresented in ecotoxicological assessments. Given their pharmacodynamic potency, environmentally relevant concentrations may induce sublethal effects in non-target organisms. In this study, we applied untargeted LC-MS-based metabolomics to investigate the sublethal effects of four widely used antidepressants—paroxetine, sertraline, fluoxetine (SSRIs), and mianserin (TeCA)—on two ecologically relevant freshwater invertebrates: S. ambiguum and D. magna. Organisms were individually exposed to each compound for 48 h at a concentration of 100 µg/L and 25 µg/L, respectively. Untargeted metabolomics captured the sublethal biochemical effects of these antidepressants, revealing both shared disruptions—e.g., in glycerophospholipid metabolism and cysteine and methionine metabolism—and species-specific responses. More pronounced pathway changes observed in D. magna suggest interspecies differences in metabolic capacity or xenobiotic processing mechanisms between taxa. Among the four antidepressants tested, sertraline in D. magna and fluoxetine in S. ambiguum exerted the most extensive metabolomic perturbations, as evidenced by the highest number and pathway impact scores. In D. magna, fluoxetine and mianserin produced similar metabolic profiles, largely overlapping with those of sertraline, whereas paroxetine affected only a single pathway, indicating minimal impact. In S. ambiguum, paroxetine and mianserin elicited comparable responses, also overlapping with those of fluoxetine, while sertraline triggered the fewest changes. These results suggest both compound-specific effects and a conserved metabolic response pattern among the antidepressants used. They also underscore the considerable potential of metabolomics as a powerful and sensitive tool for ecotoxicological risk assessments, particularly when applied across multiple model organisms to capture interspecies variations. However, further research is essential to identify which specific pathway disruptions are most predictive of adverse effects on organismal health. Full article

Memory impairment, ranging from mild memory impairment to neurodegenerative diseases such as Alzheimer’s disease, poses an escalating global health challenge that necessitates multi-targeted interventions to prevent progression. Health functional foods (HFFs), which include bioactive dietary compounds that not only provide basic nutrition but also function beyond that to modulate physiological pathways, offer a promising non-pharmacological strategy to preserve memory function. This review presents an integrative framework for the discovery, evaluation, and clinical translation of biomarkers responsive to HFFs in the context of preventing memory impairment. We examine both established clinical biomarkers, such as amyloid-β and tau in the cerebrospinal fluid, neuroimaging indicators, and memory assessments, as well as emerging nutritionally sensitive markers including cytokines, microRNAs, gut microbiota signatures, epigenetic modifications, and neuroactive metabolites. By leveraging systems biology approaches, we explore how network pharmacology, gut–brain axis modulation, and multi-omics integration can help to elucidate the complex interactions between HFF components and memory-related pathways such as neuroinflammation, oxidative stress, synaptic plasticity, and metabolic regulation. The review also addresses the translational pipeline for HFFs, from formulation and standardization to regulatory frameworks and clinical development, with an emphasis on precision nutrition strategies and cross-disciplinary integration. Ultimately, we propose a paradigm shift in memory health interventions, positioning HFFs as scientifically validated compounds for personalized nutrition within a preventative memory function framework. Full article

Zeugodacus cucuribitae (Coquillett) (Z. cucuribitae) is a global extremely invasive quarantine pest which has a wide host range of fruits and vegetables. At present, there are a few control measures for Z. cucuribitae, and deltamethrin and avermectin are commonly used. Among the hosts of Z. cucuribitae, Luffa acutangular, Luffa cylindrica, Sechium edule, Brassica oleracea var. botrytis, Musa nana, and Fragaria × ananassa are non-favored hosts. However, it is still not clear why these hosts are non-favored and whether there are any repellent components of Z. cucuribitae in these hosts. In this study, the components of these six hosts were collected from the literature, and the genes of odor and chemical sensation were determined from the genome of Z. cucuribitae. After the potential relationships between these components and genes were determined by molecular docking methods, the KEGG and GO enrichment analysis of these genes was conducted, and a complex network of genes vs. components vs. Kegg pathway vs. GO terms was constructed and used to select the key components for experiments. The results show that oleanolic acid (1 mg/mL, 0.1 mg/mL, and 0.01 mg/mL), rotenone (1 mg/mL, 0.1 mg/mL, and 0.01 mg/mL), and beta-caryophyllene oxide (1 mg/mL, 0.1 mg/mL, and 0.01 mg/mL) had a significant repellent effect on Z. cucuribitae, and three components, rotenone (1 mg/mL and 0.1 mg/mL), echinocystic acid (1 mg/mL, 0.1 mg/mL, and 0.01 mg/mL), and beta-caryophyllene oxide (1 mg/mL, and 0.1 mg/mL) had significant stomach toxicity in Z. cucuribitae. Furthermore, a complex signaling pathway was built and used to predict the effect of these components on Z. cucuribitae. These components probably play roles in the neuroactive ligand–receptor interaction (ko04080) and calcium signaling (ko04020) pathways. This study provides a reference for the prevention and control of Z. cucuribitae and a scientific reference for the rapid screening and development of new pest control drugs. Full article

Postpartum depression (PPD) remains a significant health concern worldwide. Both non-pharmacological and pharmacological treatments are available for patients with PPD; however, the standard approach involving selective serotonin reuptake inhibitors (SSRIs) and other antidepressants fails to provide a rapid response. This narrative review presents basic clinical and epidemiological data on PPD, summarizes currently used pharmacotherapies of PPD, highlights their limitations, and discusses new therapies based on a revised understanding of the disease’s pathogenesis. Numerous studies indicate that dysregulation of GABAergic neurotransmission, which may result from fluctuating levels of neuroactive steroids during pregnancy and the postpartum period, plays an important role in the complex pathology of PPD. Considering this, neuroactive steroids, which act as positive allosteric modulators of central GABA_A receptors (GABA_ARs), may offer new promising avenues for treating PPD. The first rapid-acting neurosteroid approved by the FDA to treat PPD in women is brexanolone, although its use is constrained by pharmacokinetic properties. The first oral neuroactive steroid-based antidepressant approved by the FDA for PPD is zuranolone. This review discusses the molecular mechanism of zuranolone action and the results of preclinical and clinical studies regarding the effectiveness and safety of the drug in treating PPD. Full article

Background: The gut microbiome is a key modulator of the gut–brain axis and may contribute to the pathophysiology of both gastrointestinal and systemic disorders. This study aimed to evaluate gut microbiota composition and tryptophan/phenylalanine metabolism in women with unclassified irritable bowel syndrome (IBS-U), with or without coexisting chronic fatigue syndrome (CFS). Methods: Eighty women were enrolled and divided into two groups: IBS-U without CFS (Group I, n = 40) and IBS-U with coexisting CFS (Group II, n = 40). Microbial composition and diversity were assessed using the GA-map™ Dysbiosis Test, including the dysbiosis index (DI) and Shannon Diversity Index (SDI). Hydrogen and methane levels were measured in breath samples. Urinary concentrations of selected microbial and neuroactive metabolites—homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), xanthurenic acid (XA), quinolinic acid (QA), hydroxyphenylacetic acid (HPA), and 3-indoxyl sulfate (3-IS)—were quantified using LC-MS/MS. Fatigue severity was assessed using the Chalder Fatigue Questionnaire (CFQ-11) and the fatigue severity scale (FSS). Results: Compared to Group I, patients with IBS-CFS showed significantly greater microbial diversity, higher breath methane levels, and elevated urinary concentrations of QA, XA, 3-IS, and HVA, alongside lower concentrations of 5-HIAA and KYN. Fatigue severity was positively correlated with urinary XA and QA levels. Conclusions: Women with IBS and coexisting CFS exhibit distinct gut microbiota and tryptophan metabolite profiles compared to those without fatigue. The observed metabolite–symptom associations, particularly involving neuroactive kynurenine derivatives, warrant further investigation. These preliminary findings should be interpreted as hypothesis-generating and require validation through high-resolution microbiome analyses, functional pathway profiling, and longitudinal or interventional studies to clarify causality and clinical significance. Full article

Background/Objectives: Postpartum depression (PPD) affects approximately 10–20% of women during and after pregnancy, posing significant risks to maternal health, infant development, and family dynamics. Identifying modifiable risk factors is essential for prevention. Emerging evidence suggests that vitamin D, a neuroactive steroid hormone involved in neurotransmitter synthesis, neuroinflammation regulation, and calcium homeostasis, may play a protective role against mood disorders, including PPD. Methods: The search was conducted through a comprehensive search of the PubMed, Scopus, and Web of Science databases using a combination of Medical Subject Headings (MeSH) and free-text terms including “vitamin D”, “25-hydroxyvitamin D”, “deficiency”, “pregnancy”, “postpartum”, “depression”, “antenatal depression”, “maternal mental health”, and “perinatal mood disorders”. Results: Numerous observational studies and systematic review reports around the world reinforce the potential global relevance of vitamin D insufficiency. This study advances personalized and precision medicine approaches by emphasizing the importance of individualized screening for vitamin D deficiency during pregnancy and postpartum, enabling tailored interventions that could mitigate the risk of postpartum depression. Conclusions: In conclusion, while a definitive causal relationship between vitamin D deficiency and perinatal depression remains unproven, screening for vitamin D levels during pregnancy could serve as a low-risk intervention to support maternal mental health. Future research should focus on well designed, large-scale randomized trials and standardization of diagnostic criteria to clarify vitamin D’s role in preventing perinatal depression. Recognizing vitamin D status as a modifiable biomarker allows for targeted nutritional and pharmacological strategies to optimize maternal mental health. Full article

The oral microbiome, a highly diverse and intricate ecosystem of microorganisms, plays a pivotal role in the maintenance of systemic health. With the oral cavity housing over 700 different bacterial species, the body’s second most diverse microbial community, periodontal pathogens often lead to the dysregulation of immune responses and consequently, neuropsychiatric disorders. Emerging evidence suggests a significant link between the dysbiosis of oral taxa and the progression of neurogenic disorders such as depression, schizophrenia, bipolar disorders, and more. In this paper, we show the relationship between mental health conditions and shifts in the oral microbiome by highlighting inflammatory responses and neuroactive pathways. The connection between the central nervous system and the oral cavity highlights its role as a modulator of mental health. Clinically, these findings have significant importance as dysbiosis could compromise quality of life. The weight of mental health is often compounded with treatment resistance, non-adherence, and relapse, causing a further need for treatment development. This review seeks to underscore the crucial role of the proposed oral–brain axis in hopes of increasing its presence in future intervention strategies and mental health therapies. Full article

In the treatment of ischemic stroke, an innovative approach is the use of neuroprotective compounds. Natural peptides, including adrenocorticotropic hormone (ACTH), can serve as the basis for such drugs. Previously, a significant effect of non-hormonal ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides on the functions of the nervous system was shown. Also, while using RNA-Seq, we firstly revealed differentially expressed genes (DEGs) that associated with peptides in the penumbra-associated region of the frontal cortex (FC) of rats at 24 h after transient middle cerebral artery occlusion (tMCAO) model. Peptides significantly reduced profile disturbances caused by ischemia for almost two-thousand DEGs in FC related to the neurotransmitter and inflammatory response. Here, we studied how peptides affected the expression of genes in the striatum with an ischemic focus, predominantly. The same animals from which we previously acquired FC were used to collect striatum samples. Peptides generated fewer DEGs in the striatum than in the FC. Both peptides tended to normalize the profile of disturbances caused by ischemia for hundreds of DEGs, whereas 152 genes showed an even more affected profile in the striatum under ACTH(6-9)PGP action. These DEGs were associated with inflammation, predominantly. About hundred genes were overlapped between both peptides in both tissues and were associated with neuroactive ligand-receptor interaction, predominantly. Thus, genes that are associated with the ACTH-like peptide action in rat brain regions with varying levels of ischemia injury were identified. Moreover, differential spatial regulation of the ischemia process in the rat brain at the transcriptome levels was discovered under peptides with different ACTH structures. We suppose that our results may be useful for selecting more effective neuroprotective drug structures in accordance with their specific tissue/damage therapeutic impact. Full article

Kynurenic acid (KYNA), a putative neuroprotective agent, modulates glutamatergic pathways in schizophrenia and Parkinson’s disease but is limited by acute motor activity impairments (e.g., ataxia). Research leveraging animal disease models explores its structure–activity relationship to enhance therapeutic efficacy while mitigating adverse effects, addressing global neuropsychiatric disorders affecting over 1 billion people. Structural analogs of KYNA (SZR-72, SZR-73, and SZR-81) were designed to uncouple therapeutic benefits from motor toxicity; yet, systematic comparisons of their acute behavioral profiles remain unexplored. Here, we assess the motor safety, time-dependent effects, and therapeutic potential of these analogs in mice. Using acute intracerebroventricular dosing, we evaluated motor coordination (rotarod), locomotor activity (open-field), and stereotypic behaviors. KYNA induced significant ataxia and stereotypic behaviors at 15 min, resolving by 45 min. In contrast, all analogs avoided acute motor deficits, with SZR-73 maintaining baseline rotarod performance and eliciting a delayed decrease in ambulation and inquisitiveness in open-field assays. These findings demonstrate that the structural optimization of KYNA successfully mitigates motor toxicity while retaining neuromodulatory activity. Here, we show that SZR-73 emerges as a lead candidate, combining transient therapeutic effects with preserved motor coordination. This study advances the development of safer neuroactive compounds, bridging a critical gap between preclinical innovation and clinical translation. Future work must validate chronic efficacy, disease relevance, and mechanistic targets to harness the full potential of KYNA analogs in treating complex neuropsychiatric disorders. Full article

Background: The relationship between medicinal efficacy and the geographical environment in Thesium chinense Turcz. (T. chinense Turcz.), a traditional Chinese herb, remains systematically unexplored. This study integrates metabolomics, machine learning, and ecological factor analysis to elucidate the geographical variation patterns and regulatory mechanisms of secondary metabolites in T. chinense Turcz. from Anhui, Henan, and Shanxi Provinces. Methods: Metabolomic profiling was conducted on T. chinense Turcz. samples collected from three geographical origins across Anhui, Henan, and Shanxi Provinces. Machine learning algorithms (Random Forest, LASSO regression) identified region-specific biomarkers through intersection analysis. Metabolic pathway enrichment employed MetaboAnalyst 5.0 with target prediction. Antioxidant activity (DPPH/hydroxyl radical scavenging) was quantified spectrophotometrically. Environmental correlation analysis incorporated 19 WorldClim variables using redundancy analysis, Mantel tests, and Pearson correlations. Results: We identified 43 geographical marker compounds (primarily flavonoids and alkaloids). Random forest and LASSO regression algorithms determined core markers for each production area: Anhui (4 markers), Henan (6 markers), and Shanxi (3 markers). Metabolic pathway enrichment analysis revealed these markers exert pharmacological effects through neuroactive ligand–receptor interaction and PI3K-Akt signaling pathways. Redundancy analysis demonstrated Anhui samples exhibited significantly higher antioxidant activity (DPPH and hydroxyl radical scavenging rates) than other regions, strongly correlating with stable low-temperature environments (annual mean temperature) and precipitation patterns. Conclusions: This study established the first geo-specific molecular marker system for T. chinense Turcz., demonstrating that the geographical environment critically influences metabolic profiles and bioactivity. Findings provide a scientific basis for quality control standards of geo-authentic herbs and offer insights into plant–environment interactions for sustainable cultivation practices. Full article