Brain, Behavior, and Immunity最新文献

{"title":"LXR-β regulates microglial efferocytosis and neuroinflammation in CPSP via STAT6 activation","authors":"Hu Zang, Yingjie Hu, Xiaoyu Ji, Yuye Chen, Xiao He, Li Wan, Wenlong Yao, Chuanhan Zhang, Chang Zhu, Tongtong Liu","doi":"10.1016/j.bbi.2025.106089","DOIUrl":"10.1016/j.bbi.2025.106089","url":null,"abstract":"<div><h3>Background</h3><div>Central post-stroke pain (CPSP) is a chronic neuropathic pain syndrome that develops following cerebrovascular injury and currently lacks effective treatment options. Previous research from our group has found a significant number of apoptotic cells in the thalamus of CPSP rats, and in the nervous system, the failure to promptly clear apoptotic cell debris can activate microglia, triggering a persistent neuroinflammatory response that contributes to the onset and progression of CPSP. Microglia clear apoptotic cells in the central nervous system through efferocytosis, a process that reduces neuroinflammation and promotes the reprogramming of microglia toward the M2 phenotype, which is crucial for immune defense and repair mechanisms in the central nervous system. Recent studies have shown that Liver X Receptor β (LXR-β) can regulate microglial efferocytic function, reduce neuroinflammation after intracerebral hemorrhage, and promote recovery of neurological function. In this study, we explore the potential mechanism by which LXR-β regulates microglial efferocytosis to alleviate CPSP.</div></div><div><h3>Methods</h3><div>Based on the single-cell sequencing dataset of human brain hemorrhage patients and thalamic tissue samples from rats with central post-stroke pain, a systematic analysis of the dynamic changes in efferocytosis and the associated neuroinflammation was conducted. To verify whether LXR-β regulates CPSP through efferocytosis and its potential mechanism, rats were treated with GW3965 (LXR-β agonist), GSK2033 (LXR-β inhibitor), and AS1517499 (STAT6 inhibitor), either separately or in combination. Assessments included nociceptive behavior, efferocytosis, and the expression of efferocytosis-related molecules, inflammatory factors and microglial polarization markers. In vitro experiments using BV2 cells were also performed to further elucidate the underlying mechanisms.</div></div><div><h3>Results</h3><div>Human brain hemorrhage sequencing and the CPSP rat thalamic hemorrhage model results indicated that insufficient clearance of apoptotic cells and abnormal activation of microglia were key factors contributing to abnormal neuroinflammation following a stroke. The down-regulation of LXR-β is associated with mechanical allodynia after CPSP. Activation of LXR-β enhanced efferocytosis, and upregulated efferocytosis-related molecules (MerTK, Axl, and CD36). These effects contributed to reduced neuroinflammation, promoted microglial polarization toward the M2 phenotype, and alleviated CPSP. Biological analyses and experimental results indicated that LXR-β regulated these effects through the activation of p-STAT6. In vitro studies also confirmed that the LXR-β/p-STAT6 signaling pathway is closely associated with efferocytosis and inflammation regulation in BV2 cells.</div></div><div><h3>Conclusions</h3><div>LXR-β promotes microglial efferocytosis and the expression of efferocytosis-related molecules (Mertk, Axl, and C","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106089"},"PeriodicalIF":7.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943418","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 \"Inhibition of GSDMD-dependent pyroptosis decreased methamphetamine self-administration in rats\". [Brain Behav. Immun. 120 (2024) 167-180/BBI-D-21-01152].","authors":"Yao Shen, Xinshuang Gong, Liyin Qian, Yuer Ruan, Shujun Lin, Zhaoying Yu, Zizhen Si, Wenting Wei, Yu Liu","doi":"10.1016/j.bbi.2025.106072","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.106072","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":"106072"},"PeriodicalIF":7.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943435","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":"Breakdown of blood–brain barrier, astrocytic endfeet swelling, and abnormal behaviors by blockade of TROY signaling in TROY-Fc transgenic mice","authors":"Tadasuke Komori ,&nbsp;Tomoko Hisaoka ,&nbsp;Emi Kuriyama ,&nbsp;Mizuki Kajimoto ,&nbsp;Naoyuki Nakao ,&nbsp;Toshio Kitamura ,&nbsp;Yoshihiro Morikawa","doi":"10.1016/j.bbi.2025.106083","DOIUrl":"10.1016/j.bbi.2025.106083","url":null,"abstract":"<div><div>An orphan receptor of tumor necrosis factor receptor superfamily (TNFRSF), TROY (TNFRSF19), forms the receptor complex with Nogo-66 receptor/LINGO-1 and DR6 in neurons and cerebral endothelial cells, respectively. Although TROY is expressed in astrocytes of the brain under normal conditions, its function is still unknown. Here, we demonstrated that TROY was strongly expressed in astrocytes rather than in neurons and endothelial cells in the adult mouse brain under normal conditions. Recombinant soluble form of the extracellular domain (ECD) of mouse TROY (sTROY) bound to megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1)-positive astrocytes, endfeet of which were surrounding large vessels, in the adult mouse brain. These findings suggest the presence of an unidentified ligand that directly binds to TROY in such astrocytes. To antagonize TROY ligand(s) in vivo, we generated transgenic (Tg) mice overexpressing a chimeric protein consisting of the ECD of mouse TROY and the Fc domain of human immunoglobulin G₁ (TROY-Fc). Adult TROY-Fc Tg mice showed the enhanced permeability of the blood–brain barrier (BBB), which is consistent with TROY-deficient mice, and swollen astrocytic endfeet. The expressions of tight junction proteins (claudin-5, claudin-12, occludin, and zonula occludens-1) and src-suppressed C-kinase substrate (SSeCKS) were reduced in adult Tg mice, whereas aquaporin-4 (AQP4) expression was increased. In postnatal Tg mice, the expressions of vascular endothelial growth factor and AQP4 were increased in TROY-Fc Tg mice, whereas angiopoietin-1 and SSeCKS were reduced. There was no significant change in the expression of endogenous TROY in postnatal and adult Tg mice. Behavioral tests revealed that TROY-Fc Tg mice exhibited a reduction in exploratory motivation and an enhancement of responses to stress. Thus, the signaling mediated by unidentified TROY ligand(s)-TROY interaction may be essential for proper neuronal function through the maintenance of intact BBB.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106083"},"PeriodicalIF":7.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902174","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":"Chronic ethanol exposure induces hippocampal neuroinflammation and neuronal damage via the astrocytic RUNX1/TOLLIP/TLR3 pathway","authors":"Hui Shen ,&nbsp;Qian Zhang ,&nbsp;Qing Lv ,&nbsp;Hao Liu ,&nbsp;Changliang Wang ,&nbsp;Fanyue Meng ,&nbsp;Yufu Guo ,&nbsp;Jiaxin Pei ,&nbsp;Chenyang Yu ,&nbsp;Jinming Tie ,&nbsp;Xiaohuan Chen ,&nbsp;Chaoxu Zhang ,&nbsp;Hao Yu ,&nbsp;Xiaolong Wang","doi":"10.1016/j.bbi.2025.106081","DOIUrl":"10.1016/j.bbi.2025.106081","url":null,"abstract":"<div><div>Chronic ethanol exposure (CEE) is acknowledged as a significant risk element for cognitive decline and depression, with NLRP3-related neuroinflammation identified as a crucial mechanism driving depression-like behaviors and cognitive impairment induced by CEE. Here, TLR3 is identified as a priming signal that activates NLRP3 inflammasome triggered by CEE via NF-κB p65 nuclear translocation in astrocytes. CEE-induced neuroinflammation, depressive-like behavior and cognitive impairment are alleviated by downregulation of TLR3. Mechanistically, TOLLIP, a negative regulator of TLR3 pathway, is a target gene of RUNX1, a critical transcription factor associated with inflammation. Therefore, CEE triggers NLRP3-related neuroinflammation, cognitive impairment and depressive-like behavior via RUNX1/TOLLIP/TLR3/p65 axis. Neuronal damage serves as the pathological foundation for mental disorders and is closely associated with neuroinflammatory processes. Most TLR3 in the brain is expressed in the astrocytes. Neuronal damage induced by ethanol exposure is alleviated when inflammatory reactions of astrocytes are suppressed by the inhibition of TLR3 pathway. Thus, the study offers significant insights into CEE-induced neuroinflammation and neuronal damage, as well as the relationship between these two phenomena, and offers potential therapeutic strategies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106081"},"PeriodicalIF":7.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866071","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":"Gut virome alterations in schizophrenia: identifying viral biomarkers associated with schizophrenia and treatment response","authors":"Yulu Wu ,&nbsp;Shiwan Tao ,&nbsp;Liling Xiao ,&nbsp;Jiashuo Zhang ,&nbsp;Yiguo Tang ,&nbsp;Mengting Zhang ,&nbsp;Siyi Liu ,&nbsp;Yunqi Huang ,&nbsp;Yunjia Liu ,&nbsp;Min Xie ,&nbsp;Zhengyang Zhao ,&nbsp;Qiuyue Lv ,&nbsp;Jia Cai ,&nbsp;Kean Pei ,&nbsp;Qianshu Ma ,&nbsp;Yubing Yin ,&nbsp;Minhan Dai ,&nbsp;Menghan Wei ,&nbsp;Yang Chen ,&nbsp;Qiang Wang","doi":"10.1016/j.bbi.2025.106080","DOIUrl":"10.1016/j.bbi.2025.106080","url":null,"abstract":"<div><h3>Background</h3><div>The gut virome is an important component of the microbiome with potential implications for schizophrenia. However, its role in disease pathology and treatment response remains unclear.</div></div><div><h3>Methods</h3><div>We performed metagenomic sequencing on fecal samples from 49 first-episode schizophrenia patients and 49 healthy controls. Viral diversity and taxonomic profiles were compared between groups. Within patients, we assessed associations between viral alpha diversity and symptom severity, as well as between specific viral taxa and treatment outcomes, including short- and long-term PANSS reduction and response trajectories. Response trajectories were identified by clustering patients based on the longitudinal PANSS reduction patterns.</div></div><div><h3>Results</h3><div>There were no significant differences in alpha diversity between schizophrenia patients and healthy controls. Among patients, higher viral diversity was associated with more severe negative symptoms. Although several viral taxa showed nominal associations with schizophrenia, none remained significant after FDR correction. Regarding treatment outcomes, the abundance of <em>Brigitvirus</em> was negatively associated with the 6-week symptom reduction rate (FDR = 0.012), and two viral species were reduced in the low-response trajectory group.</div></div><div><h3>Conclusions</h3><div>Although virome differences between patients with schizophrenia and healthy controls were modest, associations between viral features and both symptom severity and treatment response indicate potential clinical relevance.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106080"},"PeriodicalIF":7.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878669","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":"Developmental challenges in infants who are HIV-exposed uninfected","authors":"Lungelo Ntuli ,&nbsp;Andile Mtshali ,&nbsp;Gugulethu Mzobe ,&nbsp;Nashlin Pillay ,&nbsp;Anna-Ursula Happel ,&nbsp;Sinaye Ngcapu","doi":"10.1016/j.bbi.2025.106078","DOIUrl":"10.1016/j.bbi.2025.106078","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;The global HIV epidemic continues to affect millions of people and significantly affects children. Approximately 16 million children born to HIV-positive women, categorized as HIV-exposed uninfected (HEU), face unique developmental hurdles despite not contracting the virus. These children are more likely to experience developmental issues due to factors such as exposure to maternal HIV, antiretroviral therapy (ART), nutritional shortages, and adverse social conditions. Research indicates that children who are HIV-exposed but uninfected (HEU) may have subpar neurodevelopmental outcomes compared to those born to HIV-negative women. Despite the growing awareness of HEU children’s challenges, there remains a gap in comprehensive reviews that synthesize knowledge about the influences on their development, especially with current ART protocols. This review examines these developmental challenges, focusing on growth and neurodevelopmental outcomes; the effects of maternal HIV infection and ART; and the influence of nutrition, socio-environmental factors, and biological mechanisms on health outcomes in HEU infants.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;Children with HEU are at higher risk of growth deficits and neurodevelopmental delays. Maternal health issues, such as poor nutrition and mental health disorders, adversely affect fetal and postnatal development. Socioenvironmental conditions also shape the developmental outcomes of HEU children. In-utero exposure to HIV and antiretroviral drugs (ARVs), along with neonatal ARV exposure during breastfeeding, can negatively affect an infant’s immune function, brain structure, growth patterns, and neurodevelopment. While studies have shown differences between children born HIV-uninfected but exposed to HIV/ARV and their unexposed peers, several limitations have been noted. Much of the immunological, neurological, and mortality data in children born HIV-uninfected but exposed to HIV/ARV lacks non-HIV-exposed and ARV-exposed controls, making it challenging to distinguish between the effects of ARVs and HIV exposure. These limitations emphasize the need for future studies with well-defined control groups to isolate the effects of ARVs from HIV exposure better.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;HEU infants face multifactorial developmental challenges arising from the interplay of biological factors, including maternal immune activation, systemic inflammation, ART-related mitochondrial toxicity, and altered infant immune function and socio-environmental determinants such as nutritional deficiencies, food insecurity, and maternal mental health disorders. These interacting factors collectively impair growth, neurodevelopment, and immune competence. To mitigate these adverse outcomes, targeted interventions are urgently needed, including optimizing ART regimens to reduce infant toxicity, implementing comprehensive nutritional and food security support for mothers and children, a","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106078"},"PeriodicalIF":7.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886701","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":"Assessment of neurobehavioural traits under gnotobiotic conditions: an approach for multiple analyses in the same mouse","authors":"Andrina Rutsch ,&nbsp;Monica Iachizzi ,&nbsp;Jorum Kirundi ,&nbsp;Johan B. Kantsjö ,&nbsp;Arielle L. Planchette ,&nbsp;Terry Müller ,&nbsp;Werner Schmitz ,&nbsp;Aleksandra Radenovic ,&nbsp;Raphaël Doenlen ,&nbsp;Mercedes Gomez de Agüero ,&nbsp;Francesca Ronchi","doi":"10.1016/j.bbi.2025.106084","DOIUrl":"10.1016/j.bbi.2025.106084","url":null,"abstract":"<div><div>The gut-microbiota-brain axis influences neuroinflammation, neural development and behaviour such as sociability, memory and anxiety. To study these traits <em>in vivo</em>, especially during development or disease, it is crucial to analyse them over time and with multiple analyses in the same animal. With a growing understanding of the role of specific bacteria in neurodegenerative disease and behaviour, the demand for gnotobiotic mouse models has increased. However, maintaining stable hygienic conditions during behavioural testing is challenging, as exposure to conventional environments can alter the hygienic status of mice and affect behaviour. We established protocols to perform behavioural tests assessing memory, anxiety, exploration, learning and recognition under axenic conditions using flexible film isolators. Our study compared the behaviour of germ-free mice with mice carrying a defined minimal or moderately diverse microbiota. The results showed no effect of the microbiota on short- and long-term memory or novel object recognition. However, we showed that mice colonised with defined moderately diverse commensal bacteria exhibited more anxiety-like behaviour than germ-free mice. In addition, we showed that microbiota complexity is important, as only mice colonised with moderately diverse microbiota exhibited anxiety-like behaviour, allowing us to disentangle the contribution of specific microbial species or community interactions to this phenotype. This phenotype associated with differences in hippocampal and serum metabolic profiles between colonised and germ-free mice. We propose a novel approach to study rodent behaviour at different physiological and pathological stages in their life without compromising hygiene, thus promoting the refinement and reduction of mice used in experiments.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106084"},"PeriodicalIF":7.6,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882188","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":"Stimulation of microglia in adolescence produces a long-lasting prophylactic effect on single prolonged stress-induced PTSD-like behavior in adult mice","authors":"Rongrong Song ,&nbsp;Minxiu Ye ,&nbsp;Zhiwei Gao ,&nbsp;Xu Lu ,&nbsp;Lijun Liu ,&nbsp;Fei Cao ,&nbsp;Rongrong Yang ,&nbsp;Zhuo Chen ,&nbsp;Micona Sun ,&nbsp;Fu Li ,&nbsp;Wenfeng Hu ,&nbsp;Jie Ren ,&nbsp;Haojie Zhu ,&nbsp;Qijie Feng ,&nbsp;Chao Huang","doi":"10.1016/j.bbi.2025.106079","DOIUrl":"10.1016/j.bbi.2025.106079","url":null,"abstract":"<div><div>Our previous studies have reported that pre-stimulation of microglia in adult mice by a single injection of low-dose lipopolysaccharide (LPS) one day before stress stimulation prevents the occurrence of PTSD-like behavior induced by single prolonged stress (SPS), which disappears when the time interval between LPS injection and stress stimulation is extended to 10 days. This disappearance can be rescued by repeated LPS injection, suggesting that enhancing the response of microglia may increase stress tolerance. Since microglia exhibit strong functional plasticity during adolescence, we hypothesize that mice administered LPS during this period acquire a strong ability to resist SPS stimulation. As expected, the results showed that a single injection of LPS (100 μg/kg) on post-natal day 28 (PND28) could prevent SPS-induced development of anxiety- and fear-like behaviors and neuroinflammatory responses in the hippocampus and medial prefrontal cortex of adult mice of different ages, including PND70, PND154 and PND266. Both pre-inhibition of microglia by minocycline pretreatment and pre-depletion of microglia by PLX3397 pre-administration were able to abolish the preventive effect of low-dose LPS injection in adolescence on SPS-induced development of neuroinflammatory responses and anxiety- and fear-like behaviors in adult mice of different ages, including PND70, PND154, and PND266. These results suggest that pre-stimulation of microglia during adolescence may enable adult mice to resist harmful stress-induced PTSD-like behaviors in the long term, which could be useful for developing an approach to prevent the occurrence of PTSD from the root by a vaccine-like method.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106079"},"PeriodicalIF":7.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866070","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":"DCX+ cells cripple systemic spleen immunity and promote tumor progression","authors":"Deshan Ren ,&nbsp;Yijia He ,&nbsp;Chun Lu ,&nbsp;Yong Fu ,&nbsp;Yi Wang ,&nbsp;Qingang Hu ,&nbsp;Yanhong Ni ,&nbsp;Yuxian Song ,&nbsp;Yan Li ,&nbsp;Liang Ding","doi":"10.1016/j.bbi.2025.106076","DOIUrl":"10.1016/j.bbi.2025.106076","url":null,"abstract":"<div><div>The neuronal microtubule-associated protein doublecortin (DCX), traditionally known for its expression in neural precursor cells and its critical roles in neurogenesis and neuronal migration, has recently emerged as a potential player in cancer progression. However, its specific functions in tumor immunity remain largely unexplored. Here, we reveal a distinct central and peripheral distribution of DCX⁺ cells in human and murine cancers. In non-neurological solid tumors of human, DCX⁺ cells, as new tumor stromal components, may lack neuronal maturation capacity and exhibited a dopaminergic phenotype (NeuN⁻/CD45⁻/c-Kit⁻/CD31⁺/TH⁺/DAT⁺), and localized within highly invasive stromal microenvironments. Their presence correlated with postoperative tumor recurrence and reduced circulating CD8⁺ T cells. In 4NQO-induced murine tumor models, DCX knockdown delayed tumor progression and restored systemic antitumor immunity, characterized by diminished immunosuppressive IRF4⁺ cDC2 cells and attenuated CD8⁺ T cell exhaustion in the spleen. Notably, DCX was absent in murine tumor tissues and spleen, suggesting that DCX-mediated systemic immune regulation exclusively involved brain DCX⁺ cells, which functionally connected to peripheral sympathetic innervation of ADRB2⁺ splenic immune cells. Depletion of DCX⁺ cells downregulated splenic neurotrophins, including PGF, FGF2, GDF15, and BMPs. Even under non-tumor conditions, DCX deficiency disrupted direct sympathetic nerve-CD8⁺ T cell interactions, unleashing CD8⁺ T cell activation and intrasplenic migration. Although mechanistic differences may exist between species, our findings identify DCX⁺ cells as a novel brake on T cell activation, bridging neural and immune regulation in cancer.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106076"},"PeriodicalIF":7.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862078","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":"Transcriptional imprints of prenatal stress: sex- and time-specific signatures in early neurodevelopment","authors":"Maria Grazia Di Benedetto ,&nbsp;Moira Marizzoni ,&nbsp;Samantha Saleri ,&nbsp;Chiara Bottanelli ,&nbsp;Veronica Begni ,&nbsp;Kerstin Creutzberg ,&nbsp;Marco Andrea Riva ,&nbsp;Annamaria Cattaneo","doi":"10.1016/j.bbi.2025.106077","DOIUrl":"10.1016/j.bbi.2025.106077","url":null,"abstract":"<div><div>Prenatal stress (PNS) is a well-established animal model of foetal exposure to maternal stress and related psychiatric disorders. While its biological and behavioural effects on the offspring have been widely studied in adolescence and adulthood, early-life signatures remain largely unexplored. Here, we assessed whole-genome transcriptomic changes by RNA-sequencing, followed by pathway analyses, in hippocampi collected at postnatal day (PND)2 and PND14 from male and female rats exposed to PNS by physical maternal restraint, compared with non-stressed counterparts (n = 6 per group).</div><div>We first analysed differences between PNS animals and controls at each timepoint. At PND2, both male and female PNS animals exhibited increased synaptic activity and decreased antioxidant processes, suggesting potential accelerated neurodevelopment, excitotoxicity, and oxidative stress, which may reflect early mitochondrial dysfunction. At PND14, PNS males showed increased oxidative phosphorylation, while females displayed reduced NAD+ signalling and increased immune-related processes, collectively indicating disruptions in mitochondrial energy metabolism and redox homeostasis during the juvenile period.</div><div>Subsequently, we investigated the alterations between PND14 and PND2, focusing on those unique to PNS condition. Longitudinally, PNS animals of both sexes exhibited increased glucose and lactate metabolism, further supporting substantial alterations in mitochondrial function and energetic balance over time. Additionally, PNS males showed downregulation of cell cycle-related pathways, potentially indicating reduced neurogenesis, whereas PNS females displayed upregulated pregnenolone biosynthesis, suggesting increased steroidogenesis.</div><div>The collected findings suggest a sex- and time-dependent different modulation of multiple biological processes, with mitochondrial dysfunction emerging as a central mechanism underlying developmental programming that may predispose to future behavioural impairments.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106077"},"PeriodicalIF":7.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854679","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}