Brain, Behavior, and Immunity最新文献

{"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}

{"title":"Crosstalk between DNA damage and cGAS-STING immune pathway drives neuroinflammation and dopaminergic neurodegeneration in Parkinson’s disease","authors":"Sazzad Khan ,&nbsp;David F. Delotterie ,&nbsp;Jianfeng Xiao ,&nbsp;Ramasamy Thangavel ,&nbsp;Roderick Hori ,&nbsp;James Koprich ,&nbsp;Stephen E. Alway ,&nbsp;Michael P. McDonald ,&nbsp;Mohammad Moshahid Khan","doi":"10.1016/j.bbi.2025.106065","DOIUrl":"10.1016/j.bbi.2025.106065","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by substantial degeneration of dopaminergic neurons in the substantia nigra and dopamine depletion in the striatum, leading to debilitating motor and non-motor impairments. Recent studies provide clues on the pathogenic role of DNA damage in age-related neurodegenerative diseases, but the molecular mechanisms of DNA damage response in PD remain poorly understood. We found that the accumulation of DNA double-strand breaks (DDSBs), and/or DNA repair deficits, are key in the pathogenesis of PD and drives cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) immune regulatory pathway, contributing to neuroinflammation and dopaminergic neurodegeneration in human postmortem PD and non-PD brains as well as in experimental models of PD. We observed enhanced expression of γ-H2A.X (Ser139) a biomarker of DDSB, and decreased levels of DNA repair proteins in the brains of human PD compared to non-PD brains. This was positively correlated with upregulation of STING immune response pathways, microglial activation, senescence and dopaminergic neurodegeneration. Similarly, we observed increased and sustained DDSB as assessed by γ-H2A.X (Ser139) immunoreactivity, and degeneration of tyrosine hydroxylase-positive neurons in primary neuron/glia cultures and mice treated with 1-methyl-4-phenylpyridine (MPP+) or 1,2,3,6-tetrahydropyridine (MPTP). Next, we employed a mouse model of α-synucleinopathy, which exhibited elevated DDSBs alongside overactivation of the DNA-sensing cGAS-STING pathway and type-I interferon signaling, in association with dopaminergic neurodegeneration. Interestingly, pharmacological and genetic ablation of STING reduces DDSB, limits inflammatory response, improves behavioral function and attenuates the loss of dopaminergic neurons in this model. Our findings suggest that the accumulation of DDSBs and/or dysregulation in DNA repair proteins activate cGAS-STING mediated immune responses in the brain, potentially exacerbating dopaminergic neurodegeneration in PD. Furthermore, regulating these processes is essential for alleviating the pathological effects of PD and may offer potential therapeutic strategies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106065"},"PeriodicalIF":7.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757545","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":"Traumatic brain injury induces a sustained sensorimotor impairment associated with a dysregulated acute phase response in mice overexpressing human amyloid precursor protein","authors":"Ross E. McLeod ,&nbsp;Kush M. Kale ,&nbsp;Caroline Weglinski ,&nbsp;Anwar Masoud ,&nbsp;Naveed Akbar ,&nbsp;Fay Probert ,&nbsp;Daniel C. Anthony ,&nbsp;Jaezah Zainal","doi":"10.1016/j.bbi.2025.07.027","DOIUrl":"10.1016/j.bbi.2025.07.027","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) significantly contributes to morbidity and mortality worldwide, often leading to cognitive decline. Although there is a recognised link between TBI and the acceleration of Alzheimer’s disease (AD), the precise biological mechanisms driving this relationship are not fully understood. While several studies have investigated TBI in AD mouse models, none have examined the role of systemic inflammation in this context. In this study, we investigated the inflammatory responses, both centrally and peripherally, in 1-year-old wild-type (WT) and J20 mice (Tg:PDGFB-APPSwInd), overexpressing human amyloid precursor protein with the Swedish and Indiana mutations. Following controlled cortical impact (CCI) at 0.5 mm depth to the left somatosensory cortex, we examined outcomes at 1 and 7 days post-injury. The J20 mice exhibited a persistent sensorimotor impairment post-TBI, as determined by the adhesive removal test. Although amyloid-β42 deposition progressively increased post-injury, this behavioural deficit was not associated with greater neuronal loss compared to WT mice. Using qPCR, it was revealed that the level of proinflammatory cytokine and chemokine expression in the brain was largely conserved between WT and J20 mice, though brain <em>Cxcl10</em> expression increased by 28.6 % in J20 mice at 7d-post injury compared to WT. However, J20 mice exhibited an exaggerated acute phase response (APR) to the TBI in the liver and spleen at 7d. Accompanying the potentiated APR, ¹H NMR revealed that plasma glucose was decreased in J20 mice compared to WT at 7d. Taken together, this suggests that the sustained sensorimotor deficit in J20 mice is associated with increased amyloid-β pathology, and a dysregulated and prolonged systemic inflammatory response, accompanied by hypoglycaemia. In general, TBI in the presence of AD pathology, results in extended systemic inflammatory and metabolic responses that are likely to underpin the extended cognitive impairment, and our findings emphasise the need for customised interventions that address central and systemic inflammation after TBI in individuals with neurodegenerative disease.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 975-988"},"PeriodicalIF":7.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144757550","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":"Microglia depletion in a mouse model of prenatal and postnatal immune activation","authors":"Naomi Ciano Albanese ,&nbsp;Ignacio Del Castillo ,&nbsp;Giulia Ragaglia ,&nbsp;Giulia Castellano ,&nbsp;Maria Antonietta Ajmone-Cat ,&nbsp;Roberta De Simone ,&nbsp;Marilena Griguoli ,&nbsp;Laura Ricceri","doi":"10.1016/j.bbi.2025.07.018","DOIUrl":"10.1016/j.bbi.2025.07.018","url":null,"abstract":"<div><div>Risk for neurodevelopmental disorders can be related to early immune stimulations and altered brain microglial functions. Here we investigated the behavioural and electrophysiological effects of microglia depletion in a mouse model of developmental immune activation.</div><div>C57BL/6J pregnant mice were exposed on gestational day 12.5 to polyinosinic:polycytidylic acid (Poly I:C), subsequently, on postnatal day 9, offspring was further treated with lipopolysaccharide (LPS). At weaning, offspring was exposed throughout adolescence (4 weeks) to either a diet containing Colony Stimulating Factor-1 receptor inhibitor (PLX5622, PLX) to reduce microglia, or standard diet. Hence, we assessed i) explorative and anxiety-like responses, social responsiveness and cognitive abilities between 7^th and 8^th postnatal week; ii) synaptic transmission and neuroinflammatory and microglial molecular markers in the medial prefrontal cortex (mPFC) and hippocampus (HP) at the end of treatment (8^th postnatal week).</div><div>EIA condition reduced locomotor activity and impaired discrimination between a familiar and a novel social stimulus (social novelty response) only in male mice. Also, PLX treatment selectively affected the same social novelty response in males (both saline and EIA) and in EIA females, intriguingly sparing saline females. Unexpectedly, EIA condition <em>per se</em> did not affect spontaneous excitatory and inhibitory synaptic transmission in both mPFC and HP, whereas EIA combined with PLX reduced inhibitory transmission in males (both mPFC and HP) and neuron excitability in both male and female mPFC. Interestingly, PLX had <em>per se</em> sex- and region- specific effects increasing inhibitory transmission in female mPFC and decreasing excitatory transmission in male HP.</div><div>Molecular data, beside a robust downregulation of microglia markers in PLX diet groups, also showed that EIA condition increased interleukin-6 (<em>il-6</em>) expression in EIA males in both mPFC and HP, and elevated <em>il-1β</em> levels in both sexes in mPFC and in male HP.</div><div>Overall, these findings indicate that males have an increased vulnerability to the long-term behavioural and inflammatory effects of the EIA condition, and are more likely to exhibit behavioural and electrophysiological changes in response to microglia depletion.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 935-947"},"PeriodicalIF":7.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738914","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}