Brain, Behavior, and Immunity最新文献

{"title":"Mitigating sTNF/TNFR1 activation on VGluT2 + spinal cord interneurons improves immune function after mid-thoracic spinal cord injury","authors":"","doi":"10.1016/j.bbi.2024.10.021","DOIUrl":"10.1016/j.bbi.2024.10.021","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual’s outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-kβ dependent in VGluT2 + INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445993","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":"Stress-induced VIPergic activation mediates microbiota/Th17cell-dependent depressive-like behaviors","authors":"","doi":"10.1016/j.bbi.2024.10.016","DOIUrl":"10.1016/j.bbi.2024.10.016","url":null,"abstract":"<div><div>Chronic stress often has deleterious effects leading to the development of psychiatric diseases. The gut-brain axis represents a novel avenue for stress research. The negative effects of stress on the gut physiology have been well-described, whereas the pathways whereby stress controls microbial composition to modulate behaviors remains mainly unknown. We discovered that vasoactive intestinal peptide (VIP) activation promoted stress-induced microbial changes leading to increased infiltration of T helper (Th) 17 cells and microglial activation in the hippocampus and depressive-like behaviors, uncovering a close crosstalk between intestinal VIPergic release and the gut microbiota during stress and providing a new interaction between the nervous system and the gut microbiome after stress. Neutralization of the signature cytokine of Th17 cells, interleukin (IL)-17A, was sufficient to block depressive-like behaviors, reduce neuronal VIPergic activation and microglia activation induced by VIPergic activation after stress, opening new potential therapeutic targets for depression.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458318","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":"ApoA-I binding protein (AIBP) regulates transient receptor potential vanilloid 1 (TRPV1) activity in rat dorsal root ganglion neurons by selective disruption of toll-like receptor 4 (TLR4)-lipid rafts","authors":"","doi":"10.1016/j.bbi.2024.10.017","DOIUrl":"10.1016/j.bbi.2024.10.017","url":null,"abstract":"<div><div>Toll-like receptor 4 (TLR4) and the transient receptor potential vanilloid subtype 1 (TRPV1) are both upregulated and play key roles in the induction and expression of paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Using Apolipoprotein A-I binding protein, non-specific cholesterol depletion, TLR4 mis-sense rats and a TLR4 inhibitor, we demonstrate that co-localization of TRPV1 with TLR4 to cholesterol-rich lipid membrane rafts in nociceptors is essential for its normal activation as well as for its exaggerated activation that underlies the development and expression of CIPN. The findings suggest that TLR4-lipid rafts may have an essential role in numerous neuroinflammatory and neuropathic pain conditions. This mechanism is also generalized to female rats for the first time.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458320","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":"Extracellular vesicles: Unlocking new therapies for spinal cord injury","authors":"","doi":"10.1016/j.bbi.2024.10.010","DOIUrl":"10.1016/j.bbi.2024.10.010","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445994","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":"Association of concussion history with psychiatric symptoms, limbic system structure, and kynurenine pathway metabolites in healthy, collegiate-aged athletes","authors":"","doi":"10.1016/j.bbi.2024.10.015","DOIUrl":"10.1016/j.bbi.2024.10.015","url":null,"abstract":"<div><div>Psychiatric outcomes are commonly observed in individuals with repeated concussions, though their underlying mechanism is unknown. One potential mechanism linking concussion with psychiatric symptoms is inflammation-induced activation of the kynurenine pathway, which is thought to play a role in the pathogenesis of mood disorders. Here, we investigated the association of prior concussion with multiple psychiatric-related outcomes in otherwise healthy male and female collegiate-aged athletes (N = 212) with varying histories of concussion recruited from the community. Specially, we tested the hypotheses that concussion history is associated with worse psychiatric symptoms, limbic system structural abnormalities (hippocampal volume, white matter microstructure assessed using neurite orientation dispersion and density imaging; NODDI), and elevations in kynurenine pathway (KP) metabolites (e.g., Quinolinic acid; QuinA). Given known sex-effects on concussion risk and recovery, psychiatric outcomes, and the kynurenine pathway, the moderating effect of sex was considered for all analyses. More concussions were associated with greater depression, anxiety, and anhedonia symptoms in female athletes (ps ≤ 0.005) and greater depression symptoms in male athletes (p = 0.011). More concussions were associated with smaller bilateral hippocampal tail (ps &lt; 0.010) and left hippocampal body (p &lt; 0.001) volumes across male and female athletes. Prior concussion was also associated with elevations in the orientation dispersion index (ODI) and lower intracellular volume fraction in several white matter tracts including the in uncinate fasciculus, cingulum-gyrus, and forceps major and minor, with evidence of female-specific associations in select regions. Regarding serum KP metabolites, more concussions were associated with elevated QuinA in females and lower tryptophan in males (ps ≤ 0.010). Finally, serum levels of QuinA were associated with elevated ODI (male and female athletes) and worse anxiety symptoms (females only), while higher ODI in female athletes and smaller hippocampal volumes in male athletes were associated with more severe anxiety and depression symptoms (ps ≤ 0.05). These data suggest that cumulative concussion is associated with psychiatric symptoms and limbic system structure in healthy athletes, with increased susceptibility to these effects in female athletes. Moreover, the associations of outcomes with serum KP metabolites highlight the KP as one potential molecular pathway underlying these observations.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442409","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 \"Microbial reconstitution reverses prenatal stress-induced cognitive impairment and synaptic deficits in rat offspring\" [Brain Behav. Immun. 120 (2024) 231-247].","authors":"Jie Chen, Ru Zeng, Huimin Chen, Mengya Cao, Yihan Peng, Jianbin Tong, Jufang Huang","doi":"10.1016/j.bbi.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.bbi.2024.10.011","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458332","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":"Immunophenotyping schizophrenia subtypes stratified by antipsychotic response","authors":"","doi":"10.1016/j.bbi.2024.10.019","DOIUrl":"10.1016/j.bbi.2024.10.019","url":null,"abstract":"<div><div>Immune dysfunction has been proposed to play a role in the pathophysiology behind the development and persistence of psychosis. Current immunophenotyping studies are limited by small sample sizes and the number of immune markers investigated. Pharmacological subtypes in schizophrenia based on antipsychotic response have been proposed, but few studies have investigated immunophenotypes in treatment-resistant schizophrenia. In this study, we perform comprehensive immunophenotyping on 196 subjects comprising 147 schizophrenia patients stratified by antipsychotic response (49 antipsychotic-responsive, 70 clozapine-responsive, 28 clozapine-resistant) and 49 healthy controls. We aim to identify significant immune cell populations associated with schizophrenia and increasing treatment resistance, as potential modulators of underlying psychosis and/or treatment response. Patients with schizophrenia were recruited and assessed on the Clinical Global Impression – Schizophrenia (CGI-SCH). Treatment response was defined as a rating of three (mild severity) or less on the CGI-SCH positive symptom item after at least 8 weeks of adequate antipsychotic or clozapine treatment. Peripheral blood mononuclear cells were collected and flow cytometry was performed to identify 66 immune cell populations. Differences in cell population proportions were compared between schizophrenia cases and controls, and across all 4 groups, with <em>post-hoc</em> pairwise comparisons. Mucosal-associated invariant T (MAIT) cells (specifically CD8 + and DN double-negative subsets), total, exhausted and memory CD8 + T cells, VD1 + ϒδ T cells, plasmablasts, IgG + B cells and conventional dendritic cells 2 (cDC2) were among the top cell populations downregulated in schizophrenia. We observed increased downregulation with increasing treatment resistance. Conversely, naïve and exhausted CD4 + T cells, CD4/CD8 ratio and CCR5 + CCR2 + HLA DR + Myeloid cells were found to be upregulated in schizophrenia — we observed increased upregulation with increasing treatment resistance. We show significant immunophenotypic differences between schizophrenia cases and healthy controls, and consistent trend differences across varying degrees of antipsychotic resistance. We also examined immune cell populations not previously reported in schizophrenia. Future studies may explore immune markers identified as potential biomarkers of treatment resistance, and clarify on the relationship between immunological changes and pharmacological subtypes in schizophrenia.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458322","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":"Pericyte ablation causes hypoactivity and reactive gliosis in adult mice","authors":"","doi":"10.1016/j.bbi.2024.10.014","DOIUrl":"10.1016/j.bbi.2024.10.014","url":null,"abstract":"<div><div>Capillary pericytes are important regulators of cerebral blood flow, blood–brain barrier integrity and neuroinflammation, but can become lost or dysfunctional in disease. The consequences of pericyte loss or dysfunction is extremely difficult to discern when it forms one component of a complex disease process. To evaluate this directly, we examined the effect of adult pericyte loss on mouse voluntary movement and motor function, and physiological responses such as hypoxia, blood–brain barrier (BBB) integrity and glial reactivity. Tamoxifen delivery to <em>Pdgfrβ-CreER^T2:: Rosa26-DTA</em> transgenic mice was titrated to produce a dose-dependent ablation of pericytes <em>in vivo</em>. 100mg/kg of tamoxifen ablated approximately half of all brain pericytes, while two consecutive daily doses of 300mg/kg tamoxifen ablated &gt;80% of brain pericytes. In the open field test, mice with ∼50% pericyte loss spent more time immobile and travelled half the distance of control mice. Mice with &gt;80% pericyte ablation also slipped more frequently while performing the beam walk task. Our histopathological analyses of the brain revealed that blood vessel density was unchanged, but vessel lumen width was increased. Pericyte-ablated mice also exhibited: mild BBB disruption; increased neuronal hypoxia; astrogliosis and increased IBA1⁺ immunoreactivity, suggestive of microgliosis and/or macrophage infiltration. Our results highlight the importance of pericytes in the brain, as pericyte loss can directly compromise brain health and induce behavioural alterations in mice.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458333","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":"The effects of chronic fatigue and chronic stress on alterations in immune cell responses to acute psychosocial stress","authors":"","doi":"10.1016/j.bbi.2024.10.013","DOIUrl":"10.1016/j.bbi.2024.10.013","url":null,"abstract":"<div><div>Fatigue is a common and debilitating symptom of a broad spectrum of diseases. Previous research has shown that individuals suffering from chronic forms of fatigue experience significantly more stress compared to healthy individuals, suggesting that stress is a potential pathophysiological factor in the onset and maintenance of chronic fatigue. Individually, chronic experiences of fatigue and stress have been associated with disruptions in adaptive immunity. However, how chronic fatigue and chronic stress together affect immune regulation is not fully understood. Here, we investigated the unique and combined contribution of chronic fatigue and chronic stress on immune cell redistribution in response to, and recovery from, acute psychosocial stress. Eighty women with high or low levels of chronic fatigue and varying levels of chronic stress were exposed to a psychosocial laboratory stressor. Blood samples were collected 10 min before and then at 10, 40, and 100 min after the end of stress. The main lymphocyte subpopulations (CD3+, CD3 + CD4+, CD3 + CD8+, CD16 + CD56+, and CD19 + cells) were enumerated via flow cytometry. Acute stress resulted in an increase in CD8 + and CD16+/CD56 + cells, a decline in CD4 + cells, and no effects on CD19 + B lymphocytes. Importantly, the magnitude of immune cell redistribution during stress reactivity (CD3+, CD4+, CD16+/CD56 + ) and recovery (CD3 + ) was contingent on fatigue and chronic stress levels of individuals. Notably, in contrast to low-fatigued individuals, who showed steeper changes in cell populations, increasing levels of chronic stress did not impact immune cell migration responses in high-fatigued individuals. Our findings demonstrate the compounded blunting effects of fatigue and chronic stress on adaptive immune functioning, highlighting a potential pathway for vulnerability and detrimental effects on long-term health.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458319","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":"Ancient viral DNA in the human genome linked to neurodegenerative diseases","authors":"","doi":"10.1016/j.bbi.2024.10.020","DOIUrl":"10.1016/j.bbi.2024.10.020","url":null,"abstract":"<div><h3>Background</h3><div>Human endogenous retroviruses (HERVs) are sequences in the human genome that originated from infections with ancient retroviruses during our evolution. Previous studies have linked HERVs to neurodegenerative diseases, but defining their role in aetiology has been challenging. Here, we used a retrotranscriptome-wide association study (rTWAS) approach to assess the relationships between genetic risk for neurodegenerative diseases and HERV expression in the brain, calculated with genomic precision.</div></div><div><h3>Methods</h3><div>We analysed genetic association statistics pertaining to Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson’s disease, using HERV expression models calculated from 792 cortical samples. Robust risk factors were considered those that survived multiple testing correction in the primary analysis, which were also significant in conditional and joint analyses, and that had a posterior inclusion probability above 0.5 in fine-mapping analyses.</div></div><div><h3>Results</h3><div>The primary analysis identified 12 HERV expression signatures associated with neurodegenerative disease susceptibility. We found one HERV expression signature robustly associated with amyotrophic lateral sclerosis on chromosome 12q14 (MER61_12q14.2) and one robustly associated with multiple sclerosis on chromosome 1p36 (ERVLE_1p36.32a). A co-expression analysis suggested that these HERVs are involved in homophilic cell adhesion via plasma membrane adhesion molecules.</div></div><div><h3>Conclusions</h3><div>We found HERV expression profiles robustly associated with amyotrophic lateral sclerosis and multiple sclerosis susceptibility, highlighting novel risk mechanisms underlying neurodegenerative disease, and offering potential new targets for therapeutic intervention.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458331","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}