Brain, Behavior, and Immunity最新文献

{"title":"Temporally-regulated genetic access to IL-1β-expressing cellular networks in homeostasis and following peripheral or central immune stimuli","authors":"Daniel P. Nemeth ,&nbsp;Xiaoyu Liu ,&nbsp;Loretta Chen ,&nbsp;Margaret R. Hawkins ,&nbsp;Haroon S. Ali ,&nbsp;Madison G. Lapid ,&nbsp;Vesal Farsian ,&nbsp;Ashley Kim ,&nbsp;Julianna Saez ,&nbsp;Gabriella Maxey ,&nbsp;Numana Luqman ,&nbsp;Samantha McGovern ,&nbsp;Matt Schrier ,&nbsp;Chris Vargas ,&nbsp;Josh St. Juste-Ellis ,&nbsp;Jasmine Yip ,&nbsp;Joris Romain ,&nbsp;Adam D. Bachstetter ,&nbsp;Ning Quan","doi":"10.1016/j.bbi.2025.106177","DOIUrl":"10.1016/j.bbi.2025.106177","url":null,"abstract":"<div><h3>Background</h3><div>The proinflammatory cytokine Interleukin-1 beta (IL-1β) regulates nearly all aspects of immune function. In the brain, IL-1β is implicated in neural and immune functions under both basal and inflammatory conditions. Under basal conditions, IL-1β is known to alter sleep, memory, and affect. Under inflammatory conditions, IL-1β can induce sickness behaviors, HPA activation, and exacerbate neurological and psychological disorders. Sensitive detection and specific manipulation of IL-1β-expressing cells in the brain is currently not achievable; therefore, we generated the first mouse line to allow both robust visualization and genetic manipulation of the IL-1β-expressing cells.</div></div><div><h3>Methods</h3><div>The IL-1β-TRAP mouse was generated through Crispr9-mediated recombination. IRES-CreER^T2 was inserted following exon 7 after the stop codon of the <em>Il1b</em> gene which yielded an IL-1β-IRES-Cre-ER^T2 mouse (IL-1β-TRAP). To visualize IL-1β-expressing cells, IL-1β-IRES-Cre-ER^T2 line was crossed with ROSA26-lox-stop-lox-tdTomato mouse to generate the IL-1β-IRES-Cre-ER^T2:ROSA26-lox-stop-lox-tdTomato (IL-1β-TRAP-reporter). The IL-1β-TRAP-reporter mice were given intraperitoneal (i.p.) Tamoxifen before peripheral LPS or central IL-1β administration. PBS was used as control. The IL-1β-TRAP-reporter mice were also exposed to repetitive closed head injury (CHI) or i.p. kainic acid. tdTomato was allowed to express for 7d and distribution of IL-1β-expressing cells were observed via immunohistochemistry and/or lightsheet microscopy.</div></div><div><h3>Results</h3><div>Under basal conditions, IL-1β was found primarily to be expressed in MHCII⁺ and CD206⁺ meningeal and ventricular macrophages with sparse IL-1β-expressing microglia and neurons in brain parenchyma. Following i.p. LPS and i.c.v. IL-1β injections, IL-1β expression was found in meningeal macrophages and parenchymal P2YR12⁺ microglia. Following CHI, IL-1β-expressing macrophages increased in the meninges and IL-1β-expressing microglia were induced in the parenchyma at the injury site and along white matter tracts.</div></div><div><h3>Conclusions</h3><div>This is the first time active populations of cytokine-expressing cells are visualized, characterized, and genetically accessed using a mouse line with a knockin CreER. With this tool, we identified the choroid plexus as the predominant IL-1β-expressing region in homeostasis. Further, this mouse can be used to identify newly activated IL-1β-expressing cells; they can be targeted for manipulation in physiological and pathological contexts.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106177"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573052","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 differences in microglia morphology and function across the lifespan are mediated by the early hormone environment","authors":"Lourdes K. Davis ,&nbsp;Miranda M. Anders ,&nbsp;Steven P. Guerin ,&nbsp;Sophia E. Khoury ,&nbsp;Lindsay M. Thompson ,&nbsp;Jeffrey S. Darling ,&nbsp;Andrea C. Gore ,&nbsp;Laura K. Fonken","doi":"10.1016/j.bbi.2025.106187","DOIUrl":"10.1016/j.bbi.2025.106187","url":null,"abstract":"<div><div>Microglia, the resident immune cell of the central nervous system (CNS), contribute to a range of physiological processes across the lifespan. Microglia exhibit notable sex differences in morphology, reactivity, and transcriptomic profiles. Steroid hormones in early life are believed to elicit sex differences in many cells, including microglia, in the CNS. However, few studies have examined how neonatal hormone environment impacts microglial morphology and function across the lifespan. Therefore, here we used steroid hormones to manipulate the early hormone environment to assess the appearance and persistence of sex differences in a rat model of healthy aging. Rat pups were dosed with steroid hormones on postnatal day (P)0 and 1: females received testosterone to “masculinize” them and males received flutamide, an androgen antagonist, to “feminize” them. Brain tissue was then collected at three distinct developmental timepoints: adolescence (P30), adulthood (P150), and aging (P700) for immunohistochemistry and <em>ex vivo</em> microglial stimulation. Transcriptomic changes in hippocampal tissue of aged animals were also assessed using 3’UTR biased transcriptome sequencing (Tag-seq). We report that testosterone treatment in females leads to lifelong alterations in body size and vaginal morphology and results in microglia that display a more “masculinized” phenotype compared to controls. Flutamide had more moderate effects on microglia morphology in males, contributing to a more “feminized” phenotype in the hippocampus in adult and aged males. Testosterone treatment also resulted in greater transcriptomic changes in the aged hippocampus compared to flutamide treatment, especially in genes related to mitochondrial function and inflammation. These results indicate that (1) early hormone environment is critical for the induction of sex differences in microglial morphology and (2) sex differences in microglial morphology reverse during aging, and this reversal is also recapitulated with early hormone treatment.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106187"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573046","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":"Autophagy activation by the Becn1F121A mutation reprograms neuroinflammation and promotes neurological recovery after spinal cord injury","authors":"Zhuofan Lei,&nbsp;Yun Li,&nbsp;Hui Li,&nbsp;Junfang Wu","doi":"10.1016/j.bbi.2025.106191","DOIUrl":"10.1016/j.bbi.2025.106191","url":null,"abstract":"<div><div>Autophagy is essential for maintaining cellular homeostasis, particularly under stress conditions such as neurotrauma. In experimental models of spinal cord injury (SCI), dysregulated autophagy has been closely associated with secondary injury cascades. Our previous work demonstrated that post-injury inflammation is exacerbated by genetic inhibition of autophagy and alleviated by pharmacological enhancement. Emerging evidence also indicates that SCI can induce neuropathological changes in the brain, leading to cognitive impairments; however, the underlying molecular mechanisms remain largely unclear. In this study, we utilized Becn1^F121A/F121A knock-in (BMut) mice to investigate how genetically enhanced autophagy influences transcriptomic profiles, neural cell responses, tissue pathology, and functional recovery following contusion SCI. Transcriptomic analysis of BMut mouse spinal cord (SPC) tissues at 3 days post-injury revealed enhanced autophagy flux, reduced inflammatory responses, and altered microglial function and immune activity. Ten weeks after injury, BMut mice exhibited distinct transcriptomic profiles in the SPC, somatosensory cortex, and hippocampus. Further analyses revealed that the Becn1^F121A/F121A mutation enhanced autophagy and altered inflammatory responses to SCI across all three regions. Behavioral assessments demonstrated improved functional recovery in BMut mice, accompanied by better-preserved spared white matter and reduced lesion volume. Immunofluorescence staining analysis showed that the Becn1^F121A/F121A mutation reduced microglial activation and enhanced neurogenesis in the hippocampal dentate gyrus. Our study showed that genetic enhancement of autophagy altered transcriptomic responses, particularly inflammation, after SCI, reducing neuropathology in the spinal cord and brain and improving function. This is the first evidence linking autophagy enhancement to modulation of neuroinflammation after SCI, highlighting its therapeutic potential.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106191"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572968","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":"Searching for blood biomarkers and treatment targets in Women with fibromyalgia – Protein interaction patterns and anti-satellite glia cell IgG antibodies as promising candidates","authors":"Karolina af Ekenstam ,&nbsp;Joana Menezes ,&nbsp;Jenny E. Jakobsson ,&nbsp;Helene Silverstein ,&nbsp;Emerson Krock ,&nbsp;Jeanette Tour ,&nbsp;Katalin Sandor ,&nbsp;Alexandra Kuliszkiewicz ,&nbsp;Matthew Hunt ,&nbsp;Kim Kultima ,&nbsp;Macarena Tejos-Bravo ,&nbsp;Camilla I. Svensson ,&nbsp;Eva Kosek","doi":"10.1016/j.bbi.2025.106185","DOIUrl":"10.1016/j.bbi.2025.106185","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies suggest that autoreactive immunoglobulin G (IgG) antibodies binding to satellite glia cells (anti-SGC IgG) in the dorsal root ganglia influence pain intensity in a subgroup of fibromyalgia subjects (FMS), thus indicating altered immune activation. The main aim of this study was to identify proteins distinguishing female FMS from female healthy controls (HC) and within the FM group, proteins distinguishing FMS with high vs low levels of anti-SGC IgG. The secondary aim was to assess the associations between serum proteins and anti-SGC IgG, respectively, and FM symptoms.</div></div><div><h3>Methods</h3><div>Anti-SGC IgG was quantified using an immunofluorescence assay. Proteins in serum were assessed using Olink® Explore 384 Inflammation panel, regarding differences between FMS (n = 93) and HC (n = 40) and regarding differences between FMS with high (≥50 %) and low (&lt;50 %) anti-SGC IgG, respectively. Proteins found to differ between groups (VIP ≥ 1.3) were further analyzed regarding protein-interactions using the software tool STRING (FM vs HC n = 56, high vs low anti-SGC IgG n = 55). Results from the FM group were also compared with two nociceptive pain conditions.</div></div><div><h3>Results</h3><div>In FMS, a cluster of immune system-related proteins was found among upregulated proteins, including CD40 and CD40L, with central roles in humoral immune response. CD40 levels were associated with more severe FM symptoms. In contrast, a cluster of tissue development-/regeneration-related proteins was found among downregulated proteins, this was not seen in nociceptive pain conditions. In FMS with high anti-SGC IgG, clusters dominated by immune system-related proteins were found among both upregulated and downregulated proteins. The cluster of upregulated proteins included CD79b, a protein necessary for B-cell receptor function, and CD4, a co receptor needed for T cell activation, thus with central role in activating various immune responses, including B-cell activation. Positive correlations were seen between some of these proteins and symptoms. On the contrary, several of the downregulated proteins correlated negatively to symptoms.</div></div><div><h3>Conclusion</h3><div>Our data support the involvement of the immune system in FM and indicate that further studies on autoimmune mechanisms, proteomics, and protein interaction analysis could lead to new objective diagnostic criteria identifying FMS likely to benefit from immunomodulatory treatments.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106185"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573069","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":"Cathepsin B overexpression and lysosomal leakage in inflammatory microglia promote neuroinflammation in olfactory dysfunction by triggering mitochondrial dysfunction and pyroptosis","authors":"Huiqin Zhou ,&nbsp;Li Wang ,&nbsp;Yuanyuan Yang ,&nbsp;Fangzhou Ye ,&nbsp;Xuanyu Zhao ,&nbsp;Kesen Zhu ,&nbsp;Ziheng Huang ,&nbsp;Wei Lv ,&nbsp;Hongmeng Yu","doi":"10.1016/j.bbi.2025.106188","DOIUrl":"10.1016/j.bbi.2025.106188","url":null,"abstract":"<div><div>Olfactory dysfunction (OD) is a common sensory disorder with age-related prevalence and serves as an early clinical manifestation for neurodegenerative and inflammatory diseases. Microglia in the olfactory bulb (OB) rapidly respond to olfactory injury and initiate immune responses, but the cell state dynamics and pathways driving OD remain poorly understood. Here, we performed single-cell RNA sequencing of mouse OBs at 0, 7, and 30 days post olfactory injury, and identified 3 distinct microglial states including inflammatory, negative regulatory, and homeostatic.<!--> <!-->The inflammatory microglia exacerbated neuroinflammation by secreting cytokines and chemokines that recruited immune cells and amplify local immune responses. Cathepsin B was identified as a key regulator of this inflammatory microglial activity. In vitro studies using BV2 and primary microglia demonstrated that both pharmacological inhibition and genetic deletion of CTSB attenuated lipopolysaccharide (LPS)-induced mitochondrial dysfunction, NLRP3 activation, and pro-inflammatory cytokine release. In mice with OD, pharmacological inhibition of CTSB with CA074me promoted olfactory function recovery and modulated microglial pro-inflammatory responses. Our findings uncover inflammation-associated microglial subpopulations enriched in OD and unveiled a deleterious role for CTSB-mediated neuroinflammatory signaling in OD pathogenesis. Targeting CTSB may therefore serve as a promising therapeutic strategy to mitigate microglia-mediated neuroinflammation and facilitate olfactory recovery in OD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106188"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572971","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":"Study on the efficacy and mechanism of fecal microbiota transplantation for depression based on circadian rhythm","authors":"Pengpeng Cao ,&nbsp;Yuhao Li ,&nbsp;Shuo Zhang,&nbsp;Chuying Li,&nbsp;Yanzhuang Sun,&nbsp;Bei An","doi":"10.1016/j.bbi.2025.106186","DOIUrl":"10.1016/j.bbi.2025.106186","url":null,"abstract":"<div><h3>Background</h3><div>Depression is closely associated with disruptions in circadian rhythms, and emerging evidence highlights critical roles of gut dysbiosis in its pathogenesis. However, the mechanisms by which FMT chronotherapy influences circadian gene in depression—via gut microbiota—remain poorly understood.</div></div><div><h3>Methods</h3><div>In this study, we established a chronic unpredictable mild stress (CUMS) mouse model and performed fecal microbiota transplantation (FMT) using donor microbiota from healthy mice at two distinct circadian time points-zeitgeber time (ZT) 4 or ZT16 to identify the optimal timing for FMT based on behavioral assessments. Integrating omics dependent mechanisms of antidepressant effects mediated by these key functional bacteria.</div></div><div><h3>Results</h3><div>Health-FMT significantly alleviated depressive-like behaviors, with superior efficacy at ZT4. It restored circadian gene expressions and attenuated neuroinflammation expression in the hippocampus and prefrontal cortex. 16S rRNA sequencing revealed that Health-FMT reduced <em>uncultured_bacterium_g_Alistipes</em> abundance, a genus linked to tryptophan availability. Tryptophan supplementation regulated circadian gene expressions, inflammatory factors, brain-derived neurotrophic factors (BDNF), microglial and astrocytic activation, and exerted antidepressant effects via the ERK signaling pathway.</div></div><div><h3>Conclusions</h3><div>These findings suggest that Health-FMT exerts antidepressant effects by restoring gut homeostasis, particularly by reducing <em>Alistipes</em>, thereby rebalancing tryptophan metabolic and circadian gene expressions. These findings offer a new possible mechanism and novel insights into the microbiota-gut-brain axis in depression, and underscore the importance of chronotherapy in FMT-based therapeutic strategies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106186"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562884","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":"In utero exposure to anti-Caspr2 antibody disrupts parvalbumin interneuron function in the hippocampus","authors":"Ciara Bagnall-Moreau ,&nbsp;Joshua J. Strohl ,&nbsp;Benjamin Spielman ,&nbsp;Christian Cruz ,&nbsp;Patricio Huerta ,&nbsp;Lior Brimberg","doi":"10.1016/j.bbi.2025.106192","DOIUrl":"10.1016/j.bbi.2025.106192","url":null,"abstract":"<div><div>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in communication and social interaction and may stem from an imbalance between excitatory and inhibitory (E/I) signaling in neural circuits. Parvalbumin-expressing (PV+) interneurons are crucial for maintaining E/I balance and regulating network oscillations. Alterations in the number of PV+ interneurons or reductions in PV expression have been observed in both the postmortem brains of individuals with ASD and in animal models, including those induced by in utero exposure to maternal brain-reactive antibodies. In this study, we investigate the impact of in utero exposure to maternal anti-Caspr2 IgG on PV+ interneuron development and function in the hippocampus. Our results demonstrate a selective reduction in PV+ interneurons and perisomatic inhibitory synapses in the hippocampal CA1 region of juvenile and adult male offspring exposed in utero to anti-Caspr2 antibodies compared to controls. Additionally, local field potential (LFP) recordings from these mice show increased gamma power and altered neuronal firing patterns during social interactions, indicating functional impairments in inhibitory circuitry. These findings highlight the consequences of exposure to maternal anti-Caspr2 antibodies on PV+ interneuron development and function, providing insights into the neurobiological mechanisms underlying ASD associated behavioral phenotypes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106192"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573109","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":"Cerebral ischaemic stroke results in altered mucosal antibody responses and host-commensal microbiota interactions","authors":"Madeleine Hurry ,&nbsp;David A. Posner ,&nbsp;Raymond Wong ,&nbsp;Alba Grayston ,&nbsp;Laura Díaz-Marugan ,&nbsp;Xiaotong Zhang ,&nbsp;Bianca De Leon ,&nbsp;Corinne Benakis ,&nbsp;Ari Waisman ,&nbsp;Laura McCulloch ,&nbsp;Stuart M. Allan ,&nbsp;Catherine B. Lawrence ,&nbsp;David Brough ,&nbsp;Matthew R. Hepworth","doi":"10.1016/j.bbi.2025.106184","DOIUrl":"10.1016/j.bbi.2025.106184","url":null,"abstract":"<div><div>Stroke is a devastating neurological event with a high risk of mortality that results in long-term sequalae that extend beyond the central nervous system. Notably these include gastrointestinal dysfunction and altered composition of the commensal microbiota in both patients and mouse models, which have been suggested to contribute to secondary infection and poor clinical outcomes following stroke. Strikingly, changes in commensal microbial community composition occur rapidly following stroke and correlate with disease severity. Despite these observations, the underpinning mechanisms that drive perturbation of the microbiota post-stroke remain poorly understood. The gastrointestinal tract is home to a complex network of tissue-resident immune cells that maintain homeostatic interactions with commensal microbes and prevent bacterial-driven inflammation. Here we demonstrate mice subjected to ischaemic stroke exhibit alterations in the intestinal immune system, most notably in class switched germinal centre B cells and the production of Immunoglobulin A (IgA) – a major effector response against commensal microbes. Mice lacking secretory antibodies, including IgA, exhibited a partial reversion of stroke-induced changes in microbiota composition. Together these findings demonstrate stroke is associated with dysregulation of antibody producing immune responses, which may in part explain changes in the intestinal microbiota. A mechanistic understanding of the immunological basis of stroke-associated pathologies in the periphery may open new avenues to manage the secondary complications and long-term prognosis of patients suffering from neurological disease.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106184"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562797","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":"Diagnosis of depression in adolescence signals improved inflammatory health in adulthood: results from a nationally representative longitudinal study","authors":"Jay O’Shields ,&nbsp;George M. Slavich ,&nbsp;Orion Mowbray","doi":"10.1016/j.bbi.2025.106190","DOIUrl":"10.1016/j.bbi.2025.106190","url":null,"abstract":"<div><h3>Objective</h3><div>Childhood maltreatment increases subsequent risk for major depressive disorder (MDD), potentially through inflammatory pathways. The timely diagnosis and treatment of MDD may thus interrupt the association between inflammation and depressive symptoms, but diagnosis is frequently delayed. Additionally, sex-differences may affect timely diagnosis and treatment, contributing to differences in inflammation and depressive symptoms as individuals age.</div></div><div><h3>Method</h3><div>We used data from the nationally representative National Longitudinal Study of Adolescent to Adult Health to examine how diagnosis of MDD in adolescence vs. adulthood affected associations between childhood maltreatment, C-reactive protein (CRP) levels, and depressive symptoms in adulthood. We used path analysis to examine associations between these variables and then tested for sex differences by moderating pathways by sex.</div></div><div><h3>Results</h3><div>Childhood maltreatment increased the risk of being diagnosed with MDD at any time, and being diagnosed with MDD was associated with greater depressive symptoms in adulthood. Diagnosis of MDD at any time was associated with greater depressive symptoms, but diagnosis of MDD in adolescence was associated with lower CRP levels relative to diagnosis in adulthood. Sex differences analysis indicated that CRP was greatest for males diagnosed in adulthood despite females being diagnosed in adulthood having a greater body mass index.</div></div><div><h3>Conclusion</h3><div>Diagnosing MDD in adolescence was associated with better inflammatory health in adulthood. Timelier diagnosing and treatment of MDD after symptom onset may improve overall prognosis, particularly for males, and reduce the risk for other inflammation-related conditions.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106190"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573076","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":"Early microglia-mediated neuroinflammation after status epilepticus causes behavioral dysfunction and neurocognitive deficits but not epilepsy in mice","authors":"Peravina Thergarajan ,&nbsp;Gadeer Al-Hobaish ,&nbsp;Grace Sutherland ,&nbsp;Evelyn Tsantikos ,&nbsp;Bianca Jupp ,&nbsp;Mohammad B. Haskali ,&nbsp;Pablo M. Casillas-Espinosa ,&nbsp;Margaret L. Hibbs ,&nbsp;Terence J. O’Brien ,&nbsp;Idrish Ali ,&nbsp;Nigel C. Jones","doi":"10.1016/j.bbi.2025.106183","DOIUrl":"10.1016/j.bbi.2025.106183","url":null,"abstract":"<div><h3>Background</h3><div>Neuroinflammation is implicated in epilepsy pathogenesis, and microglia are key immune cells of the brain that participate in neuroinflammatory responses associated with epilepsy. This study investigated the role of early microglial activation following an epileptogenic brain injury on the incidence and severity of epilepsy and associated neurobehavioral impairments in a model of acquired epilepsy.</div></div><div><h3>Methods</h3><div>Status epilepticus (SE) was induced in male C57BL/6 mice via electrical stimulation of the ventral hippocampus, while additional mice were enrolled as sham controls (n = 125 total). Following termination of SE, mice received injections of the colony stimulating factor 1 (CSF1) receptor inhibitor PLX5622 (PLX; 50 mg/kg ip twice daily) to suppress microglial activation caused by SE, or vehicle, for seven days. At the end of treatment, the effect of microglial suppression on the neuroinflammatory response to SE was characterised using gene expression, immunohistochemistry, and flow cytometry. Additional mice were followed for four months and underwent a series of neurobehavioral tests and epilepsy assessment.</div></div><div><h3>Results</h3><div>PLX treatment significantly reduced Iba1 + cell counts, reduced GFAP + immunoreactivity, and downregulated the expression of proinflammatory cytokines in the hippocampus compared to vehicle following SE, intimating that the neuroinflammatory response of SE was suppressed by PLX. Flow cytometry revealed that SE significantly reduced microglial expression of CX3CR1 and CD206, but increased expression of CD16/32, shifting microglia towards a pro-inflammatory state. However, PLX treatment did not influence the relative expression of these genes. In the chronic stage, SE mice treated with PLX exhibited improved spatial memory (Y-maze test: p = 0.0016) and reduced depressive-like behavior (tail suspension test: p = 0.04; sucrose preference: p = 0.14) compared to vehicle-treated SE mice. However, PLX treatment did not alter the incidence of epilepsy after SE (58 % in vehicle treated mice vs 50 % PLX treated mice; p = 0.65) or seizure frequency in epileptic animals.</div></div><div><h3>Conclusion</h3><div>Suppression of microgliosis with PLX eliminates the neuroinflammatory response after SE, and this is associated with prevention of long-term behavioral impairment. However, this intervention does not influence the development of epilepsy. These results demonstrate that acquired epilepsy and its behavioral comorbidities have different pathogenic mechanisms after SE, with early microglial driven neuroinflammation most relevant to the latter.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106183"},"PeriodicalIF":7.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530623","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}