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No association of posttraumatic stress disorder with epigenetic aging in women at mid-life: A longitudinal cohort study 创伤后应激障碍与中年女性的表观遗传衰老无关:纵向队列研究
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-17 DOI: 10.1016/j.bbi.2024.10.003
Andrea L. Roberts , Andrew Ratanatharathorn , Lori Chibnik , Yiwen Zhu , Shaili Jha , Jae H. Kang , Erika J. Wolf , Laura D. Kubzansky , Karestan C. Koenen
{"title":"No association of posttraumatic stress disorder with epigenetic aging in women at mid-life: A longitudinal cohort study","authors":"Andrea L. Roberts ,&nbsp;Andrew Ratanatharathorn ,&nbsp;Lori Chibnik ,&nbsp;Yiwen Zhu ,&nbsp;Shaili Jha ,&nbsp;Jae H. Kang ,&nbsp;Erika J. Wolf ,&nbsp;Laura D. Kubzansky ,&nbsp;Karestan C. Koenen","doi":"10.1016/j.bbi.2024.10.003","DOIUrl":"10.1016/j.bbi.2024.10.003","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) is associated with mortality and increased risk of diseases of aging, but underlying mechanisms remain unclear. We examine associations of PTSD with one potential pathway, accelerated epigenetic aging. In a longitudinal cohort of trauma-exposed middle-aged women (n = 831, n observations = 1,516), we examined cross-sectional and longitudinal associations between PTSD, with and without comorbid depression, and epigenetic aging measured by six clocks at two time points approximately 13.5 years apart: Hannum, Horvath, PhenoAge, GrimAge, DunedinPoAM, and DunedinPACE. We further examined associations of 3 well-established predictors of aging and mortality also linked with PTSD, namely, body mass index (BMI), diet quality, and physical activity, with epigenetic aging. Cross-sectionally, across all six clocks, epigenetic aging in women with PTSD alone, depression alone, and co-occurring depression and PTSD did not differ from the reference group of women without PTSD or depression in analyses adjusted for age, self-reported race, cell proportions, and ancestry principal components. In longitudinal analyses, we similarly did not find any difference in change in epigenetic age over time by PTSD and depression status at baseline. Among the health factors, in cross-sectional analyses, higher BMI was significantly and consistently associated with greater epigenetic aging measured by the PhenoAge, GrimAge, DunedinPoAM, and DunedinPACE clocks, but not measured by the Hannum or Horvath clocks. Physical activity was not consistently associated with epigenetic aging measured by Hannum, Horvath, PhenoAge, or GrimAge. In analyses with the DunedinPoAm and DunedinPACE clocks, women who reported exercise equivalent to 1 or more hours/week walking had slower epigenetic aging than women with less exercise. Diet quality was not consistently associated with epigenetic aging measured by any of the clocks. Our data do not provide evidence that biological aging, as measured by any of the six epigenetic clocks, is a pathway linking PTSD with mortality and diseases of aging.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 672-680"},"PeriodicalIF":8.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458323","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}
引用次数: 0
Acute effects of interferon-alpha on cellular anabolic and catabolic processes are associated with the development of fatigue during Interferon-alpha-based therapy for Hepatitis-C: A preliminary study 干扰素-α对细胞合成代谢和分解代谢过程的急性影响与干扰素-α治疗丙型肝炎期间疲劳的产生有关:一项初步研究。
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-15 DOI: 10.1016/j.bbi.2024.09.038
Eva Periche-Tomas , Annamaria Cattaneo , Nadia Cattane , Claudia Bone , Jeremy Tibble , Edward T. Bullmore , Carmine Pariante , Neil A. Harrison
{"title":"Acute effects of interferon-alpha on cellular anabolic and catabolic processes are associated with the development of fatigue during Interferon-alpha-based therapy for Hepatitis-C: A preliminary study","authors":"Eva Periche-Tomas ,&nbsp;Annamaria Cattaneo ,&nbsp;Nadia Cattane ,&nbsp;Claudia Bone ,&nbsp;Jeremy Tibble ,&nbsp;Edward T. Bullmore ,&nbsp;Carmine Pariante ,&nbsp;Neil A. Harrison","doi":"10.1016/j.bbi.2024.09.038","DOIUrl":"10.1016/j.bbi.2024.09.038","url":null,"abstract":"<div><h3>Introduction</h3><div>Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis-C virus (HCV) infection. Though clinically effective, IFN-α frequently induces functionally impairing mood and motivation symptoms, particularly fatigue. Unlike mood impairment, which typically emerges after weeks of treatment, fatigue tends to emerge and evolve rapidly, typically within hours of the first IFN-α injection. Despite being a major source of functional impairment during IFN-α and other immune-based therapies, the biological mechanisms underlying fatigue remain poorly understood. Here, we aimed to identify acute immune-response signatures to IFN-α that could predict the later development of fatigue.</div></div><div><h3>Methods</h3><div>In this exploratory study, we analyzed whole blood transcriptomics in a longitudinal sample of 27 HCV patients initiating IFN-α and Ribavirin therapy. Blood samples were obtained at baseline and 4½ hours after the first IFN-α dose and transcriptomic data was obtained using Affymetrix Human Gene 1.1 ST Array Strips. Gene expression data visualization and quality control were assessed using Partek Genomics Suite V6.6 and protein–protein interaction networks using STRING and Ingenuity Pathway Analysis (IPA). A Fatigue Visual Analogue Scale (fVAS) was utilized to record fatigue symptoms at baseline, 4½ hours and 4 weeks after initiation of treatment.</div></div><div><h3>Results</h3><div>IFN-α was associated with an upregulation of 526 transcripts and a downregulation of 228 genes, indicating a rapid transcriptomic response in whole blood within 4½ hours of injection. 93 genes were significantly positively correlated with changes in fatigue, with gene expression changes measured from baseline to 4.5 h and increases in fatigue assessed from baseline to week 4 on the fVAS. We identified a novel network of predominantly cytosolic ribosomal units and ubiquitin proteins implicated in modulating mTOR signaling that was associated with the development of fatigue 4 weeks after initiation of IFN-α treatment (p = 0.0078).</div></div><div><h3>Conclusion</h3><div>Our findings suggest that acute activation of this anabolic/catabolic network by IFN-α may predispose to the experience of fatigue similar to evidence found in cancer-related fatigue. Further investigation is warranted to confirm the exploratory nature of these observations.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 717-724"},"PeriodicalIF":8.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458330","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}
引用次数: 0
Mitigating sTNF/TNFR1 activation on VGluT2 + spinal cord interneurons improves immune function after mid-thoracic spinal cord injury 减轻 VGluT2 + 脊髓中间神经元上的 sTNF/TNFR1 激活可改善中胸脊髓损伤后的免疫功能
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-15 DOI: 10.1016/j.bbi.2024.10.021
Tetyana Martynyuk , Jerome Ricard , Valerie Bracchi-Ricard , Samuel Price , Jenna R. McGrath , Kimberly J. Dougherty , Veronica Tom , John R. Bethea
{"title":"Mitigating sTNF/TNFR1 activation on VGluT2 + spinal cord interneurons improves immune function after mid-thoracic spinal cord injury","authors":"Tetyana Martynyuk ,&nbsp;Jerome Ricard ,&nbsp;Valerie Bracchi-Ricard ,&nbsp;Samuel Price ,&nbsp;Jenna R. McGrath ,&nbsp;Kimberly J. Dougherty ,&nbsp;Veronica Tom ,&nbsp;John R. Bethea","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":"123 ","pages":"Pages 633-643"},"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}
引用次数: 0
Stress-induced VIPergic activation mediates microbiota/Th17cell-dependent depressive-like behaviors 压力诱导的VIP能激活介导了微生物群/Th17细胞依赖性抑郁样行为。
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-15 DOI: 10.1016/j.bbi.2024.10.016
Eva M. Medina-Rodriguez , Dongmei Han , Shanie E. Zeltzer , Michael P. Moraskie Alvarez-Tabío , Gregory O’Connor , Sylvia Daunert , Eléonore Beurel
{"title":"Stress-induced VIPergic activation mediates microbiota/Th17cell-dependent depressive-like behaviors","authors":"Eva M. Medina-Rodriguez ,&nbsp;Dongmei Han ,&nbsp;Shanie E. Zeltzer ,&nbsp;Michael P. Moraskie Alvarez-Tabío ,&nbsp;Gregory O’Connor ,&nbsp;Sylvia Daunert ,&nbsp;Eléonore Beurel","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":"123 ","pages":"Pages 739-751"},"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}
引用次数: 0
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 载脂蛋白A-I结合蛋白(AIBP)通过选择性破坏toll样受体4(TLR4)脂质筏来调节大鼠背根神经节神经元中瞬时受体电位香草素1(TRPV1)的活性。
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-14 DOI: 10.1016/j.bbi.2024.10.017
Yan Li , Megan L. Uhelski , Robert Y. North , Luke B. Farson , Christopher B. Bankston , Gavin H. Roland , Dwight H. Fan , Katherine N. Sheffield , Amy Jia , Dana Orlando , Mario Heles , Tony L. Yaksh , Yury I. Miller , Therese A. Kosten , Patrick M. Dougherty
{"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":"Yan Li ,&nbsp;Megan L. Uhelski ,&nbsp;Robert Y. North ,&nbsp;Luke B. Farson ,&nbsp;Christopher B. Bankston ,&nbsp;Gavin H. Roland ,&nbsp;Dwight H. Fan ,&nbsp;Katherine N. Sheffield ,&nbsp;Amy Jia ,&nbsp;Dana Orlando ,&nbsp;Mario Heles ,&nbsp;Tony L. Yaksh ,&nbsp;Yury I. Miller ,&nbsp;Therese A. Kosten ,&nbsp;Patrick M. Dougherty","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":"123 ","pages":"Pages 644-655"},"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}
引用次数: 0
Extracellular vesicles: Unlocking new therapies for spinal cord injury 细胞外囊泡:开启脊髓损伤的新疗法
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-14 DOI: 10.1016/j.bbi.2024.10.010
Michelle A. Hook, Amanda H. Mahnke
{"title":"Extracellular vesicles: Unlocking new therapies for spinal cord injury","authors":"Michelle A. Hook,&nbsp;Amanda H. Mahnke","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":"123 ","pages":"Pages 631-632"},"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}
引用次数: 0
Association of concussion history with psychiatric symptoms, limbic system structure, and kynurenine pathway metabolites in healthy, collegiate-aged athletes 健康大学生运动员的脑震荡史与精神症状、边缘系统结构和犬尿氨酸途径代谢物的关系
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-14 DOI: 10.1016/j.bbi.2024.10.015
Timothy B. Meier , Jonathan Savitz , Lezlie Y. España , Bryna D. Goeckner , T. Kent Teague , Harm Jan van der Horn , L. Tugan Muftuler , Andrew R. Mayer , Benjamin L. Brett
{"title":"Association of concussion history with psychiatric symptoms, limbic system structure, and kynurenine pathway metabolites in healthy, collegiate-aged athletes","authors":"Timothy B. Meier ,&nbsp;Jonathan Savitz ,&nbsp;Lezlie Y. España ,&nbsp;Bryna D. Goeckner ,&nbsp;T. Kent Teague ,&nbsp;Harm Jan van der Horn ,&nbsp;L. Tugan Muftuler ,&nbsp;Andrew R. Mayer ,&nbsp;Benjamin L. Brett","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":"123 ","pages":"Pages 619-630"},"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}
引用次数: 0
Corrigendum to "Microbial reconstitution reverses prenatal stress-induced cognitive impairment and synaptic deficits in rat offspring" [Brain Behav. Immun. 120 (2024) 231-247]. 微生物重组可逆转大鼠后代产前应激诱导的认知障碍和突触缺陷》[Brain Behav. Immun. 120 (2024) 231-247]的更正。
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-14 DOI: 10.1016/j.bbi.2024.10.011
Jie Chen, Ru Zeng, Huimin Chen, Mengya Cao, Yihan Peng, Jianbin Tong, Jufang Huang
{"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":" ","pages":""},"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}
引用次数: 0
Immunophenotyping schizophrenia subtypes stratified by antipsychotic response 按抗精神病药反应分层的精神分裂症亚型免疫分型。
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-14 DOI: 10.1016/j.bbi.2024.10.019
Yanhui Li , Jocelyn Wen Xin Ong , Yuen Mei See , Jie Yin Yee , Charmaine Tang , Shushan Zheng , Boon Tat Ng , Bernett Teck Kwong Lee , Olaf Rotzschke , Anand Kumar Andiappan , Jimmy Lee
{"title":"Immunophenotyping schizophrenia subtypes stratified by antipsychotic response","authors":"Yanhui Li ,&nbsp;Jocelyn Wen Xin Ong ,&nbsp;Yuen Mei See ,&nbsp;Jie Yin Yee ,&nbsp;Charmaine Tang ,&nbsp;Shushan Zheng ,&nbsp;Boon Tat Ng ,&nbsp;Bernett Teck Kwong Lee ,&nbsp;Olaf Rotzschke ,&nbsp;Anand Kumar Andiappan ,&nbsp;Jimmy Lee","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":"123 ","pages":"Pages 656-671"},"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}
引用次数: 0
Pericyte ablation causes hypoactivity and reactive gliosis in adult mice 周皮消融会导致成年小鼠活动能力低下和反应性胶质细胞增多。
IF 8.8 2区 医学
Brain, Behavior, and Immunity Pub Date : 2024-10-13 DOI: 10.1016/j.bbi.2024.10.014
Jake M. Cashion , Lachlan S. Brown , Gary P. Morris , Alastair J. Fortune , Jo-Maree Courtney , Kalina Makowiecki , Dino Premilovac , Carlie L. Cullen , Kaylene M. Young , Brad A. Sutherland
{"title":"Pericyte ablation causes hypoactivity and reactive gliosis in adult mice","authors":"Jake M. Cashion ,&nbsp;Lachlan S. Brown ,&nbsp;Gary P. Morris ,&nbsp;Alastair J. Fortune ,&nbsp;Jo-Maree Courtney ,&nbsp;Kalina Makowiecki ,&nbsp;Dino Premilovac ,&nbsp;Carlie L. Cullen ,&nbsp;Kaylene M. Young ,&nbsp;Brad A. Sutherland","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<sup>T2</sup>:: 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<sup>+</sup> 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":"123 ","pages":"Pages 681-696"},"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}
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