Brain, Behavior, and Immunity最新文献

{"title":"Active coping mitigates the effects of stress on glucocorticoid levels in the prefrontal cortex","authors":"Matthew G. Frank ,&nbsp;Emily S. Levy ,&nbsp;Gianni N. Bonnici ,&nbsp;Steven F. Maier ,&nbsp;Michael V. Baratta","doi":"10.1016/j.bbi.2025.106096","DOIUrl":"10.1016/j.bbi.2025.106096","url":null,"abstract":"<div><div>Exposure to stressors elevates glucocorticoid (GC) levels in the periphery and brain, directly impacting neurogenesis, neuronal morphology and function, as well as neuroinflammatory processes. The ability to exert behavioral control over an adverse event prevents many of the sequelae of stressor exposure; however, extensive evidence indicates that this protection occurs without concomitant reductions in hypothalamic–pituitary–adrenal (HPA) axis activity. Given that brain GC levels can be regulated independently of changes in HPA output, we investigated whether controllability might alter corticosterone (CORT) levels and CORT-sensitive gene expression in rat brain, even though it does not modulate peripheral CORT. We found that behavioral control (escapable shock, ES) selectively attenuated stress-induced CORT and modulated CORT-sensitive genes (<em>Nr3c1, Ilb</em>, <em>Nlrp3</em>, and <em>Cd200r1</em>), as well as IL-1β protein in the medial prefrontal cortex (PFC) relative to uncontrollable stress (inescapable shock, IS). Stress-induced expression of PFC 11β-hydroxysteroid dehydrogenase type 1<em>,</em> an enzyme that regulates local concentrations of CORT, was increased (mRNA) and decreased (protein) in ES relative to IS. These controllability effects were absent in other brain structures previously implicated in the differential behavioral outcomes of ES and IS. Together, the findings provide initial evidence that active coping with a stressor is a key determinant for regulating GC action, potentially shaping cognitive and neuroimmune responses to adverse events at a local tissue level.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106096"},"PeriodicalIF":7.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketone monoester alleviates cognitive impairment in a transgenic mouse model of Alzheimer’s disease through innate immunological IFITM3 pathway","authors":"Tianying Zhang ,&nbsp;Jingjing Ruan ,&nbsp;Zihan Liu ,&nbsp;Yameng Yu ,&nbsp;Yirui Lu ,&nbsp;Xin Zhang ,&nbsp;Chen Hou ,&nbsp;Xiyu Liu ,&nbsp;Yuan Yuan ,&nbsp;Xiaojuan Han","doi":"10.1016/j.bbi.2025.106094","DOIUrl":"10.1016/j.bbi.2025.106094","url":null,"abstract":"<div><div>Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by irreversible cognitive decline and cerebral dysfunction, remains a major global health challenge due to elusive pathogenesis and the lack of disease-modifying therapies. Growing evidence underscores the neuroprotective potential of ketone bodies, particularly β-hydroxybutyrate (β-HB), owing to their diverse biological roles in mitigating AD-related pathology. Recent advances also implicate innate immunity in AD progression, identifying interferon-induced transmembrane protein 3 (IFITM3) as a pivotal regulator of amyloid-β (Aβ) formation. In this study, BD-AcAc2 was administered to induce exogenous ketosis in APP/PS1 transgenic mice, and Aβ-stimulated astrocytes were employed to explore the mechanistic role of β-HB as a nutritional intervention. Our findings demonstrate that β-HB significantly enhanced cognitive performance and reduced hippocampal amyloid plaque burden in APP/PS1 mice, likely through modulation of the IFITM3 pathway. Furthermore, β-HB attenuated Aβ-induced IFITM3 activation, decreased reactive oxygen species (ROS) levels, and downregulated pro-inflammatory cytokine expression in astrocytes. Collectively, these results establish β-HB as a neuroprotective agent that acts through IFITM3-mediated mechanisms, providing novel insights into therapeutic strategies targeting metabolic-immune interactions in AD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106094"},"PeriodicalIF":7.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Weissella cibaria SGW054 alleviates neurodegenerative progression in Proteus mirabilis- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease mice by regulating gut microbiota dysbiosis","authors":"Yujin Choi ,&nbsp;Yoon-Jung Shin ,&nbsp;Eugene Huh ,&nbsp;Hanbyeol Lee ,&nbsp;Siyeon Park ,&nbsp;Jin Hee Kim ,&nbsp;Seungmin Lee ,&nbsp;Young-Seo Park ,&nbsp;Myoung Gyu Park ,&nbsp;Dong-Hyun Kim ,&nbsp;Myung Sook Oh","doi":"10.1016/j.bbi.2025.106093","DOIUrl":"10.1016/j.bbi.2025.106093","url":null,"abstract":"<div><div>Emerging evidence suggests that gut microbiota dysbiosis contributes to the initial stages of neuroinflammation and dopaminergic neurodegeneration in Parkinson’s disease (PD). Probiotics are receiving attention as a treatment for PD because they restore gut microbiota balance and brain homeostasis. In this study, we demonstrated that <em>Weissella cibaria</em> SGW054 (SGW054), a probiotic strain, exhibited antibacterial activity against <em>Proteus mirabilis</em> (PM), which induces PD pathology. We evaluated the therapeutic effects of SGW054 on PD pathology in PM-induced PD model mice. Subsequently, we assessed the effects of SGW054 in mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin commonly used to induce PD, and explored its influence on gut microbiota composition. SGW054 improved motor dysfunction and neurodegeneration in PM-treated PD model mice. Additionally, SGW054 reduced microgliosis, colonic inflammatory cytokine release, gut barrier disruption, and the translocation of α-synuclein aggregates from the gut to the brain by controlling fecal PM levels. In an MPTP-induced PD mouse model, SGW054 mitigated glial hyperactivation and lowered the release of proinflammatory cytokines, such as tumor necrosis factor-α, in both the brain and colon, thereby relieving dopaminergic neuronal damage and behavioral complications. Fecal microbiota analysis demonstrated that SGW054 administration alleviated MPTP-induced microbiota dysbiosis, decreasing PM and <em>Lachnospiraceae</em> abundance while increasing probiotic bacteria levels (<em>Bacteroidaceae, Bacteroides,</em> and <em>Faecalibacterium</em>), which strongly correlated with the anti-inflammatory and neuroprotective effects of SGW054. Collectively, our findings indicate that SGW054 may serve as a novel therapeutic supplement for PD by protecting against dopaminergic neuronal loss, restoring inflammatory homeostasis, and correcting gut microbiota dysbiosis in both gut-initiated and brain-initiated PD subtypes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106093"},"PeriodicalIF":7.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration of intestinal mucosal immunity and metabolites in mice exposed to chronic restraint stress","authors":"Chujun Duan ,&nbsp;Linxiao Wang ,&nbsp;Tingting Wang ,&nbsp;Yilin Wu ,&nbsp;Niqi Shan ,&nbsp;Yuling Wang ,&nbsp;Hanyin Fan ,&nbsp;Yangmengjie Jing ,&nbsp;Kun Cheng ,&nbsp;Lin Liu ,&nbsp;Ran Zhuang","doi":"10.1016/j.bbi.2025.106090","DOIUrl":"10.1016/j.bbi.2025.106090","url":null,"abstract":"<div><div>Depression is greatly impacted by stress. Individuals with depression are more susceptible to developing gastrointestinal disorders. Chronic restraint stress (CRS) can induce depression-like behaviors in animals. However, the effects of CRS on intestinal mucosal immunity and metabolism, which may play roles in modulating depression-like behaviors, are not yet fully understood. A C57/BL6J mouse model of CRS was established to induce depression-like behaviors. Histopathological and cell biology techniques were used to assess intestinal mucosal changes. Transcriptome sequencing of ileum and colon tissues and nontargeted metabolomics of colonic contents were performed to analyze gene and metabolite alterations after CRS. The study findings revealed that CRS mice had disturbed mucosal microenvironments, as evidenced by increased crypt depths and inflammation scores, enhanced intestinal permeability, and reduced expression of defensins. At the mucosal effector sites, the proportion of TCRαβ⁺CD8αβ⁺ intraepithelial lymphocytes (IELs) in the epithelium and innate lymphoid cells type 3 (ILC3s) in the lamina propria was notably reduced. Transcriptome sequencing revealed the enrichment of differential genes in lipid metabolic processes, particularly in steroid metabolism. Metabolomic analysis further revealed that 28-homobrassinolide, 1α,25-dihydroxy-11α-phenylcholecalciferol, and 2α-α(benzyloxy)-1α,25-dihydroxy-19-norcholecalciferol, all belonging to steroid hormones, were significantly decreased after CRS. Given that the latter two are side chain-modified 1,25-dihydroxyvitamin D3 (1,25D3), intervention with 1,25D3 was implemented in CRS mice. The results were promising as 1,25D3 treatment not only improved the depression-like behavior but also enhanced the intestinal mucosal immune milieu. Notably, 1,25D3 intervention significantly increased the proportion of TCRαβ⁺CD8αβ⁺ IELs in CRS mice, which may be the inner cause to enhance mucosal defense. Additionally, microbiota sequencing provided valuable evidence for the resource and regulation of differential metabolites. Hence, our study suggests a potential role of steroid metabolism in chronic stress-induced intestinal mucosal disorders and provides preliminary evidence supporting the therapeutic effects of 1,25D3 on depression combined with gastrointestinal disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106090"},"PeriodicalIF":7.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific metabolic and central effects of GLP-1–estradiol conjugate in middle-aged rats on a standard or western diet","authors":"Jennifer E. Richard ,&nbsp;Ahmad Mohammad ,&nbsp;Kimberly A. Go ,&nbsp;Andrew J. McGovern ,&nbsp;Rebecca K. Rechlin ,&nbsp;Tallinn F.L. Splinter ,&nbsp;Stephanie E. Lieblich ,&nbsp;Lara K. Radovic ,&nbsp;Lydia Feng ,&nbsp;Samantha A. Blankers ,&nbsp;Bin Yang ,&nbsp;Jonathan D. Douros ,&nbsp;Brian Finan ,&nbsp;Liisa A.M. Galea","doi":"10.1016/j.bbi.2025.106088","DOIUrl":"10.1016/j.bbi.2025.106088","url":null,"abstract":"<div><div>Middle age represents a critical window for metabolic and cognitive health, particularly in the context of rising obesity and diabetes rates. Glucagon-like peptide-1 (GLP-1)-based therapies, which regulate blood glucose and body weight, show sex-specific effects, with estradiol potentiating their metabolic benefits. However, research on GLP-1′s cognitive and neuroprotective roles has largely been conducted in males. Here, we investigated the effects of GLP-1 conjugated to estradiol (GE2) on metabolism, cognition, cytokine levels and neurogenesis in the dentate gyrus of middle-aged male and female rats fed a standard (SD) or Western (WD) diet. In both sexes, WD increased body weight and plasma leptin levels, regardless of sex. GE2 treatment led to weight loss, enhanced cued and contextual fear memory, reduced cytokine levels in the hippocampus in SD rats, and increased neurogenesis in the dorsal dentate gyrus (DG), regardless of sex. Sex-specific differences were observed in fat distribution, glucose regulation, central cytokine levels, and neuroplasticity after WD and GE2 treatment. In females only, GE2 reduced visceral (gonadal) fat, reduced cytokines in the dorsal hippocampus, and improved basal blood glucose in response to a WD. In males only, GE2 restored neurogenesis in the DG after WD exposure, and reduced cytokine levels in the amygdala. These findings suggest that although WD increased body weight and GE2 improved associative learning in both sexes, both WD and GE2 had differential affects on metabolic hormones, insulin regulation, cytokine levels and neuroplasticity. Our findings underscore the importance of sex-specific approaches in metabolic and neuroprotective therapeutics in middle age.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106088"},"PeriodicalIF":7.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal exposure to advanced oxidation protein products induces neurodevelopmental abnormalities in the offspring of mice","authors":"Jiexing He ,&nbsp;Qian Chen ,&nbsp;Mingzheng Zhu ,&nbsp;Yanxuan Xiao ,&nbsp;Qiuyu Huang ,&nbsp;Ailan Yin ,&nbsp;Sijia Jiang ,&nbsp;Pei Zhu ,&nbsp;Tingyu Xiang ,&nbsp;Jing Li ,&nbsp;Zhongjun Li ,&nbsp;Xinping Yang ,&nbsp;Mei Zhong","doi":"10.1016/j.bbi.2025.106091","DOIUrl":"10.1016/j.bbi.2025.106091","url":null,"abstract":"<div><div>Preeclampsia (PE) not only causes multi-organ damage to the mother but also exerts long-term effects on the development of the offspring. Prenatal exposure to PE has been demonstrated to result in deleterious neurodevelopment and behavioral abnormalities in the offspring. Our prior research has evidenced that advanced oxidation protein products (AOPPs), both the biomarker and promoter of oxidative stress, contribute to the pathogenesis of preeclampsia by inducing trophoblast dysfunction and systemic inflammation. However, it remains unclear whether offspring mice exposed to placental oxidative stress and dysfunction induced by AOPPs will exhibit abnormal neurodevelopment and the underlying mechanisms involved. In this study, we found pregnant mice injected with AOPPs and AOPPs-induced sEVs exhibited PE-like symptoms with elevated blood pressure and reduced fetal weight. Furthermore, behavioral detection showed that male and female adult offspring mice exposed to AOPPs prenatally displayed impairments in learning and memory. Placental and hippocampal transcriptome sequencing revealed that inflammation and immune response may play a pivotal role in this process. Our study provides valuable insights into the pathogenesis of adverse neurodevelopment and cognitive dysfunction in offspring exposed to placental oxidative stress induced by AOPPs and the search for effective preventive and therapeutic measures.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106091"},"PeriodicalIF":7.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrimination and dendritic cell abundance among older adults in the health and retirement study","authors":"Jemar R. Bather ,&nbsp;Emiko O. Kranz ,&nbsp;Mariana Rodrigues ,&nbsp;Steven W. Cole ,&nbsp;Adolfo G. Cuevas","doi":"10.1016/j.bbi.2025.106087","DOIUrl":"10.1016/j.bbi.2025.106087","url":null,"abstract":"<div><div>We investigated whether peripheral blood dendritic cell (DC) abundance varies as a function of discrimination exposure in a national sample of older US adults (aged 50 + years) from the 2016 Venous Blood Study, a US Health and Retirement Study biomarker project. Density of myeloid DCs (mDC) and plasmacytoid DCs (pDC) were measured using multiparameter flow cytometry. Discrimination was assessed using the validated Everyday Discrimination Scale. Weighted linear regression models quantified associations between discrimination and natural-log transformed DC abundance, controlling for sociodemographic factors, chronic health conditions, and health behaviors. We tested whether these associations varied by race/ethnicity. For mDC, we found no significant overall association with discrimination. However, race/ethnicity significantly modified this relationship: among non-Hispanic White participants, a 1-SD increase in discrimination was associated with a non-significant 1.4 % increase in mDC count (<em>p</em> = 0.20), while non-Hispanic Black participants showed a significant 4.6 % decrease (interaction <em>p</em> = 0.021). For pDC, a 1-SD change in discrimination was significantly associated with a 2.4 % increase in abundance across all participants (95 % CI: 0.6 %, 4.3 %, <em>p</em> = 0.010), with no significant effect modification by race/ethnicity. In this nationally representative study of older Americans, discrimination exposure was associated with altered dendritic cell abundance, with distinct patterns by cell type and race/ethnicity. Increased pDC counts across all racial/ethnic groups suggest a common immunological response to discrimination, while divergent mDC responses between non-Hispanic Black and White participants indicate race-specific immune modulation. These findings reveal complex cellular pathways through which discrimination may differentially influence immune function and contribute to health inequities.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106087"},"PeriodicalIF":7.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a highly simplified microbiota on postnatal intestinal, immune, and brain development","authors":"Hannah Sturgeon ,&nbsp;Alexandra Castillo-Ruiz ,&nbsp;Emem Ukpong ,&nbsp;Lavanika Praveen ,&nbsp;Gina Leyva ,&nbsp;Benoit Chassaing ,&nbsp;Nancy G. Forger","doi":"10.1016/j.bbi.2025.106085","DOIUrl":"10.1016/j.bbi.2025.106085","url":null,"abstract":"<div><div>At birth, the newborn mammal enters a highly microbial world, leading to colonization of the gut by trillions of microorganisms, known as the microbiota. We previously reported that germ-free (GF) mice have altered brain development in the first days of life, suggesting that the arrival of microbes at birth is essential for normal brain development. However, GF mice are a highly artificial model system, with known deficits in immune and intestinal development. To determine the effects of a more realistic curtailment of microbial exposure, we utilized a reduced, defined microbiota. Specifically, GF mouse dams were colonized with the altered Schaedler flora (ASF), a community of eight bacterial species, which supports relatively normal immune and intestinal function in adulthood. Measures in the periphery (colon histology and gene expression, plasma cytokines) and brain (neuronal cell death, microglial density, forebrain expression of cytokine and blood–brain barrier protein genes) were then compared among offspring born to ASF, GF, and conventionally colonized (CC; i.e., control) mice at postnatal day (P)3 or P23, focusing on those measures previously reported to differ between CC and GF conditions. We observed that ASF newborns have a higher bacterial load in the colon than CC mice but are essentially monocolonized. For some measures (e.g., plasma cytokines, neuronal cell death), ASF newborns at P3 are similar to controls, whereas for others they are GF-like or intermediate. The ASF microbiota grows to comprise 5 bacterial species by weaning age, compared to explosive diversification in CC offspring. Analyses at P23 demonstrate that microglia density is like that of controls in ASF weanlings but several peripheral measures remain GF-like. Thus, effects of an absent microbiota are evident within a few days of life, and colonization with a highly simplified, defined microbiota normalizes some, but not all, measures in the developing periphery and brain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106085"},"PeriodicalIF":7.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colonoscopic fecal microbiota transplantation for Mild-to-Moderate Parkinson’s Disease: A randomized controlled trial","authors":"Jingyi Wang ,&nbsp;Liujun Xue ,&nbsp;Minna Zhang ,&nbsp;Peng Shen ,&nbsp;Wenzhuo Zhao ,&nbsp;Qiang Tong ,&nbsp;Shangnong Wu ,&nbsp;Weijie Dai ,&nbsp;Xiaozhong Yang ,&nbsp;Honggang Wang","doi":"10.1016/j.bbi.2025.106086","DOIUrl":"10.1016/j.bbi.2025.106086","url":null,"abstract":"<div><h3>Objective</h3><div>Growing evidence supports the efficacy and safety of fecal microbiota transplantation (FMT) in treating Parkinson’s disease (PD). Fecal microbiota are commonly transplanted via oral capsules, a nasojejunal tube, or colonoscopy, but freezing often decreases the diversity and viability of transplanted microbiota. This single-center, double-blind, randomized, placebo-controlled trial aims to explore the efficacy and safety of fresh FMT via colonoscopy in dealing with PD.</div></div><div><h3>Methods</h3><div>Thirty patients with mild-to-moderate PD (Hoehn-Yahr stage I-III) were randomly assigned into the FMT group (fresh FMT via colonoscopy) and placebo group (saline injection via colonoscopy) in a 1:1 ratio. Motor and non-motor symptoms, constipation, quality of life, cognitive function, emotional state and sleep quality were assessed using relevant scales. Fecal samples were harvested before and at 4, 8 and 12 weeks after treatment for metagenomic and metabolomics analyses.</div></div><div><h3>Results</h3><div>A total of 30 patients with mild-to-moderate PD were enrolled in the present study, involving 18 males and 12 females with a median age of 68 years, a median age of onset of 63.5 years, and a median disease duration of 3 years. At 12 weeks, scores of the UPDRS Ⅲ (group × time effect, B =  − 8.80 [−13.79, −3.81]), PAC-QOL (group × time effect, B =  − 29.67 [−45.35, −13.98]), UPDRS Ⅱ (group × time effect, B =  − 5.07 [−8.85, −1.28]), NMSS (group × time effect, B =  − 35.60 [−53.59, −17.61]), PDQ-39 (group × time effect, B =  − 17.80 [−28.21, −7.39]), HAMA (group × time effect, B =  − 1.66 [−2.92, −0.40]), and HAMD (group × time effect, B =  − 1.33 [−2.49, −0.16]) were significantly reduced in the FMT group, while CSBM per week (group × time effect, B = 3.03 [1.42, 4.63]) and the Bristol Stool Scale score (group × time effect, B = 1.95 [0.12, 3.79]) significantly increased (all <em>P</em> &lt; 0.05). Significant alterations were seen in the gut microbiota and fecal metabolites in the FMT group. No adverse events were observed during the follow-up period.</div></div><div><h3>Conclusion</h3><div>Fresh FMT via colonoscopy is a safe and well-tolerated procedure for treating mild-to-moderate PD. It effectively alleviates motor and non-motor symptoms, thus facilitating defecation and improving the quality of life. These effects can be maintained for a minimum of 12 weeks and may be attributed to the optimization of gut microbiota and fecal metabolites.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106086"},"PeriodicalIF":7.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"hADMSC-Evs attenuates depressive and anxiety − like behaviors in chronic liver disease via suppressing Liver-Brain Galectin3 signaling","authors":"Wenjun Fu ,&nbsp;Yanan Guo ,&nbsp;Peiru Wu ,&nbsp;Lvyao Xiao ,&nbsp;Wenxin Qi ,&nbsp;HongCui Cao ,&nbsp;Naijun Dong ,&nbsp;Robert Chunhua Zhao ,&nbsp;Jiao Wang","doi":"10.1016/j.bbi.2025.106082","DOIUrl":"10.1016/j.bbi.2025.106082","url":null,"abstract":"<div><div>Chronic liver disease (CLD) is strongly associated with depression, affecting approximately 18–58% of patients and significantly worsening clinical outcomes. Although human adipose-derived mesenchymal stem cell extracellular vesicles (hADMSC-Evs) have demonstrated therapeutic potential in CLD, their ability to simultaneously alleviate depression in CLD remains unexplored. Here we report that hADMSC-Evs administration effectively attenuates both liver fibrosis and depression-like behavior in CLD mice. In addition, hADMSC-Evs treatment restored prefrontal cortical synaptic plasticity impairments observed in CLD mice. Integrated RNA-seq analysis and experimental validation identified hADMSC-Evs suppressed liver-brain Galectin3 signalling in CLD mice. Mechanistic investigations revealed that elevated circulating Galectin3 potentiates microglia-mediated synaptic pruning through complement pathway activation, thereby compromising synaptic structural integrity and promoting anxiety and depression-like phenotypes. This study provides mechanistic evidence supporting hADMSC-Evs as a dual-target therapeutic vehicle for CLD and its neuropsychiatric complications, while proposing Galectin3 mediated liver-brain axis dysregulation as a novel pathogenic mechanism underlying CLD-related depression. Our findings further highlight the therapeutic potential of modulating interorgan communication pathways through extracellular vesicle-based interventions.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106082"},"PeriodicalIF":7.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}