Brain, Behavior, and Immunity最新文献

{"title":"Variations in executive function in toddlers after exposure to pre-pregnancy overweight and obesity and the mediating role of inflammation in a longitudinal pregnancy cohort study","authors":"Min Xu ,&nbsp;Ping Zu ,&nbsp;Shuang-Shuang Ma ,&nbsp;Hai-Xia Wang ,&nbsp;Nan Jiang ,&nbsp;Jing-Feng Bian ,&nbsp;Ji-Rong Xu ,&nbsp;Wei Luo ,&nbsp;Peng Zhu","doi":"10.1016/j.bbi.2025.106075","DOIUrl":"10.1016/j.bbi.2025.106075","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to determine the association between pre-pregnancy overweight and obesity status in pregnant women and executive function (EF) development in toddlers and establish whether inflammatory biomarkers mediate this association.</div></div><div><h3>Methods</h3><div>This prospective cohort included 1,126 mother-infant pairs. Pre-pregnancy body mass index (ppBMI) was obtained from medical records, and the participants categorized into normal weight, overweight and obese groups according to standard ppBMI classifications. Toddlers’ EF scores were assessed using the Behaviour Rating Inventory of Executive Functioning Preschool Version (BRIEF-P), with higher scores reflecting worse EF. Linear regression models were used to compared EF scores between toddlers of normal weight mothers and those of overweight and obese mothers. The mediating effects of mid-pregnancy inflammatory biomarkers were analyzed using the SPSS PROCESS plug-in.</div></div><div><h3>Results</h3><div>Compared with pre-pregnancy normal weight, pre-pregnancy overweight and obesity was associated with EF related behavioral dysfunction in the domains of inhibition (<em>β</em> = 3.20, 95 % confidence interval [CI]: 0.92, 5.48), shifting (<em>β</em> = 3.12, 95 % CI: 0.88, 5.36), emotional control (<em>β</em> = 3.44, 95 % CI: 1.18, 5.71), working memory (<em>β</em> = 4.17, 95 % CI: 1.87, 6.47) and planning/organization (<em>β</em> = 3.19, 95 % CI: 0.93, 5.45) in toddlers. Analysis of the association between high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) levels in mid-pregnancy and EF in toddlers demonstrated that only hs-CRP was positively associated with EF (Global Executive Composite score, <em>β</em> = 0.28, 95 % CI: 0.07, 0.49). Mediation analysis revealed that maternal hs-CRP levels in mid-pregnancy mediated 17.4 % of the association between ppBMI and EF in toddlers, with an indirect effect of 0.75 (95 % CI: 0.31, 1.24) and a direct effect of 3.56 (95 % CI: 2.55, 4.58).</div></div><div><h3>Conclusions</h3><div>Pregnant women with pre-pregnancy overweight and obesity were more likely to have toddlers with worse EF, and mid-pregnancy maternal hs-CRP levels partially mediated this association. Future studies should explore whether improving the pro-inflammatory metabolic milieu in pregnancies complicated by excess weight could reduce the likelihood of increased EF related behavioral dysfunction.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106075"},"PeriodicalIF":7.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831339","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":"Prebiotics improve motor function, cognition and gut health in a preclinical model of Huntington’s disease","authors":"Millicent N. Ekwudo ,&nbsp;Bethany Masson ,&nbsp;Madeleine R. Di Natale ,&nbsp;Pamudika Kiridena ,&nbsp;Nicholas van de Garde ,&nbsp;Enie Lei ,&nbsp;Sujan Kumar Sarkar ,&nbsp;Vinod K. Narayana ,&nbsp;Thibault Renoir ,&nbsp;John B. Furness ,&nbsp;Carolina Gubert ,&nbsp;Anthony J. Hannan","doi":"10.1016/j.bbi.2025.106074","DOIUrl":"10.1016/j.bbi.2025.106074","url":null,"abstract":"<div><div>Huntington’s disease (HD) is a currently incurable neurodegenerative disorder characterised by psychiatric, cognitive and motor deficits, as well as peripheral manifestations, including gastrointestinal (GI) and immunological impairments. The R6/1 mouse model of HD, expressing a mutant human <em>huntingtin</em> transgene, exhibits excellent construct and face validity. Evidence of gut dysbiosis has been reported in clinical and preclinical HD and is strongly associated with disease symptoms, including cognitive and behavioural outcomes. Recently, high dietary fibre was shown to rescue cognitive and affective deficits and improve gut function in HD mice, by unknown mechanisms. Hence, we aimed to evaluate the therapeutic potential of gut microbial modulation by prebiotics in the treatment of HD. Given the well-documented role of prebiotics such as fructooligosaccharide (FOS) and galactooligosaccharide (GOS) as substrates of beneficial microbes, we hypothesised that chronic supplementation of FOS + GOS (PREB intervention) would ameliorate the gut dysbiosis associated with HD and consequently attenuate other deficits in this preclinical model.</div><div>Here, R6/1 HD mice and wild-type (WT) littermate controls were randomised to receive PREB or vehicle (drinking water) from 6-20 weeks of age. We assessed the onset and progression of motor, cognitive and affective deficits, as well as GI parameters and gut macroscopy. Additionally, we profiled the gut microbiota in faecal samples collected at week 14 (using 16S rRNA gene sequencing) and assessed their derivatised short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs).</div><div>Compared to vehicle controls, PREB improved the motor performance of female HD mice and enhanced the cognitive performance of female HD and WT mice. Furthermore, PREB increased caecal weight (both sexes), stool softness (females) and faecal levels of SCFAs, including butyrate (males), acetate (both sexes) and propionate in both HD and WT males but female HD mice only. The prebiotics intervention also decreased gut transit time in females at late onset and faecal output in both HD and WT males at early onset, as well as juxtauterine fat (in females). Furthermore, PREB decreased α-diversity and increased β-diversity in both sexes, including a remarkable increase in SCFA-producing microbes such as <em>Bifidobacterium animalis</em> in PREB-treated animals. Taken together, PREB effectively modulated the HD core phenotype, particularly motor coordination, cognition and GI parameters as described above, and remodelled the gut microbiota of HD mice.</div><div>This prebiotic intervention has a strong safety profile and is directly translatable to future clinical trials of HD. Our findings suggest that targeting the gut microbiota in HD is a plausible clinical strategy and may inform novel therapeutic approaches to delay the onset and/or progression of this debilitating condition and other neurological disorders","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106074"},"PeriodicalIF":7.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844480","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":"Specific viral antibodies associate with anti-NMDAR encephalitis after herpes simplex encephalitis","authors":"Jakob Kreye ,&nbsp;William R. Morgenlander ,&nbsp;Manjusha Thakar ,&nbsp;Poul M. Schulte-Frankenfeld ,&nbsp;Sarah Schott ,&nbsp;Isabel Bünger ,&nbsp;Hans-Christian Kornau ,&nbsp;Julia W. Angkeow ,&nbsp;Sahana Jayaraman ,&nbsp;Carolin Otto ,&nbsp;Wiebke Hahn ,&nbsp;Jan Lewerenz ,&nbsp;Franziska S. Thaler ,&nbsp;Mirjam Korporal-Kuhnke ,&nbsp;Nico Melzer ,&nbsp;Justina Dargvainiene ,&nbsp;Christian G. Bien ,&nbsp;Rose Kohlie ,&nbsp;Erik Lattwein ,&nbsp;Dietmar Schmitz ,&nbsp;H. Benjamin Larman","doi":"10.1016/j.bbi.2025.106073","DOIUrl":"10.1016/j.bbi.2025.106073","url":null,"abstract":"<div><div>Herpes simplex encephalitis (HSE) patients may develop secondary anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (NMDARE), associated with worsened long-term neurological outcome. Immunosuppressive treatment can limit NMDAR autoantibody-mediated pathology, but early predictive biomarkers for the risk of NMDARE are lacking. In a multicenter study, we performed unbiased antibody reactome profiling using Phage ImmunoPrecipitation Sequencing (PhIP-Seq). HSE patients with secondary NMDARE (n = 13) versus those without (n = 10) showed enhanced antibody responses against HSV-1, but not HSV-2, which comprised specific antibodies to five peptides of the HSV-1 UL42 and UL48 proteins. A score of these signature CSF antibodies identified HSE patients with secondary NMDARE with a sensitivity of 75%, a specificity of &gt; 99%, a positive predictive value of 90%, a negative predictive value of &gt; 97% and an odds ratio (OR) of 209 (CI: 28 – 1,582) across all individuals in this study, and with similar performance values in serum (&gt;66%, &gt;99%, &gt;88%, &gt;96%, OR 307 (15 – 6,089)). These signature antibodies represent a promising biomarker to identify HSE patients at risk for NMDARE development. In NMDARE patients without a history of HSE and in MS patients, no disease-associated HSV antibody reactivity patterns were detected. Furthermore, we introduced the Multiplexed Index Calculations of the Antibody Reactome (MICAR) metric to characterize proteomic targets of compartment-specific antibody responses, an approach that is applicable in neuroimmunology and other compartmentalized disease states.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106073"},"PeriodicalIF":7.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844481","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":"Corrigendum to \"Preconditioning to mild oxidative stress mediates astroglial neuroprotection in an IL-10-dependent manner\" [Brain Behav. Immun. 30 (2013) 176-185].","authors":"Niva Segev-Amzaleg, Dorit Trudler, Dan Frenkel","doi":"10.1016/j.bbi.2025.106067","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.106067","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":"106067"},"PeriodicalIF":7.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834014","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":"Parylation dependent nuclear export of HMGB1 via exportin 1 contributes to morphine tolerance","authors":"Ying-Ping Liang ,&nbsp;Da-Ying Zhang ,&nbsp;Dong-Sheng Le ,&nbsp;Li Liu ,&nbsp;Fan Yang ,&nbsp;Shi-Yu Sun ,&nbsp;Guo-Rong Lai ,&nbsp;Chao Zhang ,&nbsp;Mai-Lin Zhao ,&nbsp;Ping-Sheng Liao ,&nbsp;Tong Liu ,&nbsp;Bing Wang","doi":"10.1016/j.bbi.2025.106070","DOIUrl":"10.1016/j.bbi.2025.106070","url":null,"abstract":"<div><h3>Background</h3><div>Nucleocytoplasmic transport has been implicated in chronic pain, particularly through importin-mediated nuclear import. However, the role of nuclear export in opioid-induced adaptations remains unclear. Exportin 1 (XPO1), a key nuclear export protein, has not been studied in the context of morphine tolerance. This study explores the contribution of XPO1 and its interaction with pro-inflammatory mediators in the development of opioid tolerance and hyperalgesia.</div></div><div><h3>Methods</h3><div>A rat model of chronic morphine administration was used to assess changes in spinal XPO1 expression and activity. Phosphorylation status of XPO1 and upstream kinases were evaluated by immunoblotting. Proteomic analysis of cerebrospinal fluid (CSF) was performed to identify secreted factors associated with morphine exposure. Co-immunoprecipitation and in vitro assays were used to examine the interaction between XPO1 and high mobility group box 1 (HMGB1). The role of PARP1-mediated poly(ADP-ribosyl)ation (PARylation) in regulating HMGB1 nuclear export was also investigated. Behavioral assays were used to assess the impact of pharmacological inhibition of XPO1 and PARP1 on morphine tolerance and nociceptive hypersensitivity.</div></div><div><h3>Results</h3><div>Chronic morphine exposure led to significant upregulation of XPO1 in spinal neurons, accompanied by phosphorylation at serine 1010 by serine/threonine kinase 38 (STK38), which enhanced its nuclear export function. CSF proteomics revealed elevated levels of HMGB1, a pro-inflammatory mediator. XPO1 inhibition suppressed HMGB1 secretion. Mechanistically, PARP1-mediated PARylation of HMGB1 was essential for its interaction with XPO1 and subsequent nuclear export. Combined low-dose inhibition of XPO1 and PARP1 reversed established morphine tolerance and alleviated mechanical hypersensitivity. However, intrathecal administration of recombinant HMGB1 abolished these effects, reinstating morphine tolerance.</div></div><div><h3>Conclusions</h3><div>These findings reveal a novel mechanism by which STK38-driven phosphorylation of XPO1 and PARP1-mediated modification of HMGB1 coordinate nuclear export and extracellular signaling in the context of opioid tolerance. Dual inhibition of XPO1 and PARP1 represents a promising therapeutic strategy to suppress neuroinflammation and enhance opioid analgesic efficacy.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106070"},"PeriodicalIF":7.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811818","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":"Biopsychosocial correlates of resting and stress-reactive salivary GDF15: preliminary findings","authors":"Cynthia C. Liu ,&nbsp;Caroline Trumpff ,&nbsp;Qiuhan Huang ,&nbsp;Robert-Paul Juster ,&nbsp;Martin Picard","doi":"10.1016/j.bbi.2025.106068","DOIUrl":"10.1016/j.bbi.2025.106068","url":null,"abstract":"<div><div>Growth differentiation factor 15 (GDF15) is a biomarker of energetic stress related to aging, disease, and mitochondrial defects. We recently showed that GDF15 is quantifiable in saliva and acutely inducible by psychosocial stress. To date, the associations between GDF15 and biopsychosocial factors and individual characteristics remain unknown. Here, in a sample of healthy working adults (<em>n</em> = 198, 70 % females), we first confirmed that salivary GDF15 reacts to acute psychosocial stress, peaking 10 min following a socio-evaluative stress paradigm (+28.3 %, <em>g</em> = 0.50, <em>p</em> &lt; 0.0001). We then explored associations between i) resting/baseline GDF15 and ii) GDF15 stress reactivity and a variety of trait- and state-level biopsychosocial factors including sex and gender characteristics; measures of mental health, stress, and burnout; physical health and health behaviors; and anthropometric and blood-based metabolic biomarkers. Baseline salivary GDF15 was higher in men than in women and was positively correlated with testosterone, while negatively correlated with estrogen and traditionally feminine gender roles. Of the psychosocial factors examined, we found that work-related stress variables were most consistently related to GDF15, with work-related cynicism, burnout, and emotional exhaustion predicting higher GDF15 reactivity, while job-related autonomy and utilization of competence predicted smaller GDF15 responses. Consistent with GDF15′s induction in metabolic and renal diseases, baseline GDF15 was also positively correlated with indirect markers of metabolic disease including waist-to-hip ratio, creatinine, and albumin. Finally, participants with greater GDF15 reactivity also exhibited greater cortisol reactivity, consistent with the role of GDF15 in stress regulation and energy mobilization. Together, this exploratory analysis of salivary GDF15 suggest new biological and psychosocial correlates, calling for large-scale studies connecting human experiences with biological markers of energetic stress.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106068"},"PeriodicalIF":7.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811817","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":"Microglial involvement in autism spectrum disorder: insights from human data and iPSC models","authors":"Susanne Michels,&nbsp;Akash Mali,&nbsp;Henna Jäntti,&nbsp;Mohammad Rezaie,&nbsp;Tarja Malm","doi":"10.1016/j.bbi.2025.106071","DOIUrl":"10.1016/j.bbi.2025.106071","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) presents a range of lifelong challenges in social communication, repetitive behaviors, and restricted interests, affecting over 2% of the preschool population. Early neurodevelopmental disruptions, particularly those affecting microglia, appear to be central to the pathophysiology of ASD, with microglia influencing synaptic development and stability in the brain. However, the neurobiological mechanisms underlying ASD are still not fully understood. Traditional ASD studies, which rely on animal models and postmortem tissues, have limitations in capturing human-specific neurodevelopmental dynamics. Recent advances in human model systems, including induced pluripotent stem cell (iPSC)-derived neural cultures and brain organoids, offer promising insights into microglia-neuron interactions relevant to ASD. This review evaluates current research using human-based models to explore ASD pathophysiology, focusing on the role of microglia in neurodevelopment, and discusses the strengths and future potential of these innovative approaches.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106071"},"PeriodicalIF":7.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803591","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":"Influenza A virus infection during pregnancy increases transfer of maternal bloodborne molecules to fetal tissues","authors":"Rafael J. Gonzalez-Ricon ,&nbsp;Ashley M. Otero ,&nbsp;Izan Chalen ,&nbsp;Jeffrey N. Savas ,&nbsp;Shakirat Adetunji ,&nbsp;Adrienne M. Antonson","doi":"10.1016/j.bbi.2025.106069","DOIUrl":"10.1016/j.bbi.2025.106069","url":null,"abstract":"<div><div>Influenza A virus (IAV) infection during pregnancy is linked to heightened risk for neurodevelopmental disorders (NDDs) in the offspring. The precise pathophysiological mechanism(s) underling this association remains an active topic of research. We propose that maternal immune activation (MIA) triggered by IAV infection can disrupt selective permeability at the maternal-fetal interface, leading to increased transfer of blood-derived molecules into the fetal compartment. Some of these molecules might be responsible for the initiation of inflammatory cascades implicated in NDD etiology. Using a murine model of seasonal IAV infection during pregnancy, we examined placental and fetal brain barrier properties following maternal IAV challenge. Our findings demonstrate an enhanced transplacental transfer of fluorescently labeled tracers from maternal circulation to key neurodevelopmental regions, including the subventricular zone (SVZ) and choroid plexus (ChP) of fetal brains. This effect was most pronounced in fetuses from dams exposed to the highest dose of IAV. Notably, a similar pattern was observed for accumulation of the bloodborne neuroinflammatory molecule fibrinogen in these same brain regions, which was further amplified in response to the highest IAV dose. Moreover, fibrinogen accumulation was positively correlated with Iba1⁺ cell immunofluorescence, suggesting a potential interaction between fibrinogen and Iba1⁺ cells. Collectively, these findings suggest that IAV-induced MIA enhances transplacental transfer of blood-derived molecules into fetal tissues, potentially activating proinflammatory pathways in Iba1⁺ cells.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106069"},"PeriodicalIF":7.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803590","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":"A screen of immune signaling molecules regulated by neuronal activity identifies interferon-gamma as a modulator of synaptic function and anxiety-like behavior","authors":"Renu Heir ,&nbsp;Malak Abuzgaya ,&nbsp;Houaria Adaïdi,&nbsp;Marie Franquin,&nbsp;Zahra Abbasi,&nbsp;David Stellwagen","doi":"10.1016/j.bbi.2025.106066","DOIUrl":"10.1016/j.bbi.2025.106066","url":null,"abstract":"<div><div>A number of immune signaling molecules have been shown to act within the central nervous system to regulate neuronal function. To look for additional candidates, we conducted a screen of the expression of immune signaling molecules regulated by neuronal activity in the hippocampus. Hippocampal slice cultures were treated for 48 h with TTX (to block neuronal activity) or gabazine (to block GABA-A receptors and thus elevate neuronal activity). These treatments are known to trigger homeostatic synaptic plasticity, and regulate the expression of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF). The screen revealed a number of immune signaling molecules were upregulated by TTX, and a smaller subset upregulated by gabazine. We validated some of the more prominent responders, including Interferon gamma (IFNγ). We then tested the effects of IFNγ on synaptic function. IFNγ could acutely alter both glutamatergic and GABAergic synaptic function, and mice with deficient IFNγ signaling have altered anxiety-like behaviour, although only in males. These data support the idea that many signaling molecules initially characterized in the immune system have important endogenous regulatory roles within the CNS under non-pathological conditions.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106066"},"PeriodicalIF":7.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783487","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":"Perinatal morphine exposure induces long-term changes in the intestinal microbiota of male and female rats.","authors":"Hannah J Harder, Charlène J G Dauriat, Benoit Chassaing, Anne Z Murphy","doi":"10.1016/j.bbi.2025.106064","DOIUrl":"10.1016/j.bbi.2025.106064","url":null,"abstract":"<p><p>The increased use of opioids by women of reproductive age has resulted in a dramatic rise in the number of infants exposed to opioids in utero. Although perinatal opioid exposure (POE) has been associated with an elevated risk of infection and hospitalization later in life, the mechanisms by which opioids influence immune development and maturation are not fully elucidated. Alterations in the intestinal microbiota composition, which lead to changes in immune training and maturation, could be at play. Chronic opioid use in adults is associated with a proinflammatory and pathogenic microbiota composition; therefore, we hypothesized here that in utero morphine exposure could negatively affect intestinal microbiota composition, leading to alterations in immune system function. We report that a clinically-relevant model of perinatal opioid exposure, in rats, induces profound intestinal microbiota dysbiosis that is maintained into adulthood. Furthermore, microbial maturity was reduced in morphine-exposed offspring. This suggests that the increased risk of infection observed in children exposed to opioids during gestation may be a consequence of microbiota alterations with a downstream impact on immune system development. Further investigation of how perinatal morphine induces dysbiosis will be critical to the development of early life interventions designed to ameliorate the increased risk of infection observed in these children.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":"106064"},"PeriodicalIF":7.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}