Brain, Behavior, and Immunity最新文献_第4页

Microglia specific Csf1r haploinsufficiency induces depressive-like behaviors by promoting NLRP6/caspase-1 signaling in mice 小鼠小胶质细胞特异性Csf1r单倍不足通过促进NLRP6/caspase-1信号传导诱导抑郁样行为

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-17 DOI: 10.1016/j.bbi.2025.04.015

Rui-Kang Pang , Jia-Yi Zheng , Hao-You Xu , Yuan-Qi Zhao , Shan Su , Kai Le , Ye-Feng Cai , Shi-Jie Zhang , Xiao-Xiao Li

{"title":"Microglia specific Csf1r haploinsufficiency induces depressive-like behaviors by promoting NLRP6/caspase-1 signaling in mice","authors":"Rui-Kang Pang , Jia-Yi Zheng , Hao-You Xu , Yuan-Qi Zhao , Shan Su , Kai Le , Ye-Feng Cai , Shi-Jie Zhang , Xiao-Xiao Li","doi":"10.1016/j.bbi.2025.04.015","DOIUrl":"10.1016/j.bbi.2025.04.015","url":null,"abstract":"<div><div>Depression is an early clinical manifestation of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), although the underlying molecular mechanisms remain poorly elucidated. The objective of this study was to investigate the mechanisms underpinning depressive behavior in the context of ALSP, utilizing microglial-specific <em>Csf1r</em> haploinsufficient mice. Our findings indicate that these mice exhibited depressive-like behaviors, as well as microglial hyper-ramification and aberrant synaptic pruning capacity. Blockade of CSF1R signaling with PLX3397 resulted in significant amelioration of depressive symptoms and restoration of normal microglial morphology and function. RNA sequencing analysis of microglia isolated from the medial prefrontal cortex (mPFC) of the brain indicated that NLRPs signaling pathways may play a significant role in the observed alterations in microglial <em>Csf1r</em> haploinsufficient mice. Notably, NLRP6, rather than NLRP3, was found to be upregulated, and the expression of caspase-1 exhibited colocalization with the microglial marker Iba1. Pharmacological inhibition of caspase-1 using VX-765 improved depressive-like behaviors, as well as microglial function. Taken together, our findings delineate a causal relationship between microglial <em>Csf1r</em> haploinsufficiency-induced activation of the NLRP6/caspase-1 signaling pathway and the manifestation of depressive-like behaviors in ALSP mice.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 383-399"},"PeriodicalIF":8.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859174","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

CMPK2 facilitates pain sensitization by promoting the lactylation and deactivation of cGAS-STING pathway in neuropathic pain 在神经性疼痛中，CMPK2通过促进cGAS-STING通路的乳酸化和失活来促进疼痛致敏

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-17 DOI: 10.1016/j.bbi.2025.04.016

Mei Yang , Erliang Kong , Honghao Song , Xiaochen Zhang , Xudong Feng , Tong Hua , Huawei Wei , Qianbo Chen , Hongbin Yuan

{"title":"CMPK2 facilitates pain sensitization by promoting the lactylation and deactivation of cGAS-STING pathway in neuropathic pain","authors":"Mei Yang , Erliang Kong , Honghao Song , Xiaochen Zhang , Xudong Feng , Tong Hua , Huawei Wei , Qianbo Chen , Hongbin Yuan","doi":"10.1016/j.bbi.2025.04.016","DOIUrl":"10.1016/j.bbi.2025.04.016","url":null,"abstract":"<div><div>Neuropathic pain, a complex condition arising from nerve damage, presents significant challenges in pain management, driving extensive research into its molecular mechanisms. Our mRNA microarray analysis identified cytosine monophosphate kinase 2 (CMPK2) as a key player in the progression of neuropathic pain, but the molecular mechanism remains to be elusive. By western blotting and <em>Q</em>-PCR, we observed a notable upregulation of CMPK2, particularly in microglia of the spinal dorsal horn during neuropathic pain. <em>In vivo</em> and <em>in vitro</em> experiments demonstrated that <em>Cmpk2</em> deficiency significantly alleviated neuropathic pain and neural injury by increasing the production of type I interferons (IFN-I), which are known for their analgesic properties. Conversely, overexpression of <em>Cmpk2</em> in microglia led to a marked decrease in IFN-I production <em>in vitro</em>. Further investigation revealed that the transcription factor RUNX1 promoted CMPK2 upregulation in microglia. Mechanistically, we found that CMPK2 exacerbated neuropathic pain by enhancing glycolysis in microglia, resulting in increased lactate production. This accumulation of lactate induced lactylation and deactivation of the stimulator of interferon genes (STING), which was responsible for IFN-I production. These findings suggested that CMPK2 facilitated pain sensitization by promoting microglial glycolysis, resulting in the increased lactylation and deactivation of the cGAS-STING pathway in neuropathic pain, highlighting the potential of targeting CMPK2 for therapeutic intervention in neuropathic pain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 370-382"},"PeriodicalIF":8.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855710","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 "Microbiome-derived indole-3-lactic acid reduces amyloidopathy through aryl-hydrocarbon receptor activation" [Brain Behav. Immun. 122 (2024) 568-582]. “微生物衍生的吲哚-3-乳酸通过芳基烃受体激活减少淀粉样变性”的更正[脑行为]。免疫学杂志。122(2024)568-582。

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-17 DOI: 10.1016/j.bbi.2025.03.033

Hyun Kim, Eunkyung Lee, Mincheol Park, Kyungchan Min, Yen N Diep, Jinhong Kim, Hyeok Ahn, Eulgi Lee, Sujeong Kim, Yunjae Kim, You Jung Kang, Joon Hyung Jung, Min Soo Byun, Yanghyun Joo, Chanyeong Jeong, Dong Young Lee, Hansang Cho, Hansoo Park, Tae Kim

引用次数: 0

Sustained NPSLE-like phenotype in the absence of systemic lupus-like disease in TLR7-deficient B6.Nba2 mice 缺乏tlr7的B6在没有系统性狼疮样疾病的情况下持续npsl样表型Nba2老鼠

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-15 DOI: 10.1016/j.bbi.2025.04.017

Audrey Kwun , James K. Sullivan , John Shelestak , Kayla M. Merritt , Selena S. Liu , Gabrielle Mey , Tara DeSilva , Trine N. Jørgensen

{"title":"Sustained NPSLE-like phenotype in the absence of systemic lupus-like disease in TLR7-deficient B6.Nba2 mice","authors":"Audrey Kwun , James K. Sullivan , John Shelestak , Kayla M. Merritt , Selena S. Liu , Gabrielle Mey , Tara DeSilva , Trine N. Jørgensen","doi":"10.1016/j.bbi.2025.04.017","DOIUrl":"10.1016/j.bbi.2025.04.017","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the role of Toll-like Receptor 7 (TLR7) in the development of neuropsychiatric lupus (NPSLE) in the B6.Nba2 murine model of SLE.</div></div><div><h3>Methods</h3><div>TLR7-deficient B6.Nba2 mice were evaluated for the development of NPSLE symptoms through behavioral testing with comparison groups of wild-type NPSLE-prone B6.Nba2 and B6 controls. Behavioral testing results were evaluated in the context of biomarker data, including flow cytometry for immune cell activation, and enzyme-linked immunosorbent assays (ELISA) to measure serum cytokine and autoantibody levels, including autoantibodies against double stranded DNA (dsDNA) and DWEYS peptide. Brain and spleen tissues waere harvested, and immuno histochemical studies and inflammatory gene activation obtained via qPCR were further analyzed to characterize immune system activation and SLE and NPSLE development in the mice.</div></div><div><h3>Results</h3><div>TLR7-deficient mice exhibited reduced signs of systemic SLE, including decreased splenomegaly, anti-dsDNA titers, and immune cell activation compared to wild-type mice. However, TLR7-deficient mice displayed a similar behavioral pattern to the NPSLE-prone B6.Nba2 mice, indicating NPSLE development was not influenced by TLR7. Knockout of TLR7 in B6.Nba2 mice also led to increased expression of TLR4 and TLR9, which suggests a possible role for these receptors in NPSLE pathogenesis.</div></div><div><h3>Conclusion</h3><div>While systemic lupus-like disease in the B6.Nba2 mouse model is dependent on TLR7, NPSLE development is not and may be influenced by TLR4 and TLR9 signaling. Thus, there may be separate mechanisms driving peripheral SLE compared to NPSLE with possible implications for pharmacologic management.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 352-361"},"PeriodicalIF":8.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850475","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

Noradrenergic signaling controls Alzheimer’s disease pathology via activation of microglial β2 adrenergic receptors 去甲肾上腺素能信号通过激活小胶质β2肾上腺素能受体控制阿尔茨海默病的病理

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-15 DOI: 10.1016/j.bbi.2025.04.022

L.H.D. Le , A.M. Feidler , L. Calcines Rodriguez , M. Cealie , E. Plunk , H. Li , K. Kara-Pabani , C. Lamantia , M.K. O’Banion , A.K. Majewska

{"title":"Noradrenergic signaling controls Alzheimer’s disease pathology via activation of microglial β2 adrenergic receptors","authors":"L.H.D. Le , A.M. Feidler , L. Calcines Rodriguez , M. Cealie , E. Plunk , H. Li , K. Kara-Pabani , C. Lamantia , M.K. O’Banion , A.K. Majewska","doi":"10.1016/j.bbi.2025.04.022","DOIUrl":"10.1016/j.bbi.2025.04.022","url":null,"abstract":"<div><div>Norepinephrine (NE) is a potent anti-inflammatory agent in the brain. In Alzheimer’s disease (AD), the loss of NE signaling heightens neuroinflammation and exacerbates amyloid pathology. NE inhibits surveillance activity of microglia, the brain’s resident immune cells, via their β2 adrenergic receptors (β2ARs). Here, we investigate the role of microglial β2AR signaling in AD pathology in the 5xFAD mouse model of AD. We found that loss of cortical NE projections preceded the degeneration of NE-producing neurons and that microglia in 5xFAD mice, especially those microglia that were associated with plaques, significantly downregulated β2AR expression early in amyloid pathology. Importantly, dampening microglial β2AR signaling worsened plaque load and the associated neuritic damage, while stimulating microglial β2AR signaling attenuated amyloid pathology. Our results suggest that microglial β2AR could be explored as a potential therapeutic target to modify AD pathology.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 307-322"},"PeriodicalIF":8.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843629","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

Traveling to the brain: Intestinal dendritic cells as early mediator of gut microbiota − innate immune system Axis 前往大脑：肠道树突状细胞作为肠道微生物群-先天免疫系统轴的早期介质

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-15 DOI: 10.1016/j.bbi.2025.04.023

Stefano Farioli Vecchioli

引用次数: 0

PNIRS Society Announcements PNIRS协会公告

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-14 DOI: 10.1016/S0889-1591(25)00142-4

引用次数: 0

Inducing elevated glucose levels in vitro: A model to simulate prediabetes (preDBT) states in primary cultures 体外诱导葡萄糖水平升高：在原代培养中模拟前驱糖尿病（preDBT）状态的模型

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-14 DOI: 10.1016/j.bbi.2025.04.019

Canal Maria Pilar , Acutain Maria Florencia , Nini Karen Agustina , Munner Mariana , Caruso Ornella , De Tomas-Liorio Anna , Badollati Adelina , Baez María Verónica

{"title":"Inducing elevated glucose levels in vitro: A model to simulate prediabetes (preDBT) states in primary cultures","authors":"Canal Maria Pilar , Acutain Maria Florencia , Nini Karen Agustina , Munner Mariana , Caruso Ornella , De Tomas-Liorio Anna , Badollati Adelina , Baez María Verónica","doi":"10.1016/j.bbi.2025.04.019","DOIUrl":"10.1016/j.bbi.2025.04.019","url":null,"abstract":"<div><div>There is increasing evidence suggesting a relationship between prediabetes (preDBT, the early stage of Type 2 Diabetes or DBT2) and neurodegenerative disorders (NDDs) such as Alzheimer’s disease. The preDBT stage, characterized by impaired fasting glucose (IFG), may represent an early risk factor for cognitive decline and the onset of NDDs. However, the underlying mechanisms connecting preDBT to cognitive impairment and neurodegeneration remain poorly understood. This study aims to explore the effects of IFG on central nervous system (CNS) cells by developing an in vitro model of preDBT using sera from individuals with IFG. Our results demonstrate that exposure of astrocyte-neuron mixed cultures to IFG sera induced hyperglycemia, increased oxidative levels and astrogliosis that would lead to cognitive impairment observed in the analyzed cohort, as evidenced by a battery of cognitive tests. These findings suggest that the early stages of preDBT may trigger changes in CNS cells that correlate with cognitive decline. The study underscores the importance of early diagnosis and intervention in preDBT to prevent progression to DBT2 and associated NDDs.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 323-335"},"PeriodicalIF":8.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843630","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

Effects of a mild inflammatory challenge on cytokines and sickness behavior: A randomized controlled trial using the influenza vaccine 轻度炎症对细胞因子和疾病行为的影响：一项使用流感疫苗的随机对照试验

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-14 DOI: 10.1016/j.bbi.2025.04.018

Tatum A. Jolink , Mallory J. Feldman , Natalie M. Antenucci , Megan N. Cardenas , Taylor N. West , Zev M. Nakamura , Keely A. Muscatell

{"title":"Effects of a mild inflammatory challenge on cytokines and sickness behavior: A randomized controlled trial using the influenza vaccine","authors":"Tatum A. Jolink , Mallory J. Feldman , Natalie M. Antenucci , Megan N. Cardenas , Taylor N. West , Zev M. Nakamura , Keely A. Muscatell","doi":"10.1016/j.bbi.2025.04.018","DOIUrl":"10.1016/j.bbi.2025.04.018","url":null,"abstract":"<div><div>The influenza vaccine has reliably been associated with mild, within-person increases in inflammation. However, the field lacks rigorous experimental work comparing the effects of the influenza vaccine to a placebo control on changes in plasma inflammatory cytokines and self-reported sickness behavior. In a double-blind, randomized, placebo-controlled trial, 102 participants received either the influenza vaccine or saline placebo. Four cytokines were measured in plasma 24-hours following injection; participants also reported on psychosocial outcomes, specifically sickness behavior, positive/negative affect, sleep, and subjective social disconnection. All cytokines—IL-6, IL-10, TNF-α, IFN-γ—were significantly increased in the influenza vaccine condition compared to placebo. None of the psychosocial outcomes differed by condition. This study fills a gap in the literature by presenting critical causal evidence that the influenza vaccine leads to elevated levels of four inflammatory cytokines, compared to placebo control. However, a more robust increase in inflammation or a larger sample size may be necessary to observe differences in self-reported sickness behavior and other psychosocial outcomes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 429-439"},"PeriodicalIF":8.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874412","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

Dr. Steven F. Maier: A fearless scientist, a rigorous mentor, and a legacy of excellence Steven F. Maier博士：一位无畏的科学家，一位严谨的导师，以及卓越的遗产

IF 8.8 2区医学

Brain, Behavior, and Immunity Pub Date : 2025-04-13 DOI: 10.1016/j.bbi.2025.04.021

Ruth M. Barrientos , Michael V. Baratta , Matthew G. Frank

引用次数: 0