Pub Date : 2025-02-01DOI: 10.1016/j.bbi.2024.12.007
Evrim Gökçe , Thomas Freret, Antoine Langeard
Maintaining physical function is crucial for independent living in older adults, with gait speed being a key predictor of health outcomes. Blood biomarkers may potentially monitor older adults’ mobility, yet their association with slow gait speed still needs to be explored. This study aimed to investigate the relationship between blood biomarkers and gait speed using the Midlife in the United States (MIDUS) study biomarker dataset. A cross-sectional design was employed for analysis, involving 405 individuals aged 60 years and over. We used a machine learning framework, specifically the XGBoost algorithm, feature selection methods, and the Shapley Additive Explanations, to develop an explainable prediction model for slow gait speed. Our model demonstrated the highest cross-validation score with the six most important features among 35 variables, as elevated interleukin-6, C-reactive protein, glycosylated hemoglobin, interleukin-8, older age, and female sex were significantly associated with reduced gait speed (area under the curve = 0.75). Our findings suggest that blood biomarkers can play a critical role in integrated models to assess and monitor slow gait speed in older adults. Identifying key blood biomarkers provides valuable insights into the underlying physiological mechanisms of mobility decline and offers promising avenues for early intervention to preserve mobility in the aging population.
{"title":"Blood Biomarker Signatures for Slow Gait Speed in Older Adults: An Explainable Machine Learning Approach","authors":"Evrim Gökçe , Thomas Freret, Antoine Langeard","doi":"10.1016/j.bbi.2024.12.007","DOIUrl":"10.1016/j.bbi.2024.12.007","url":null,"abstract":"<div><div>Maintaining physical function is crucial for independent living in older adults, with gait speed being a key predictor of health outcomes. Blood biomarkers may potentially monitor older adults’ mobility, yet their association with slow gait speed still needs to be explored. This study aimed to investigate the relationship between blood biomarkers and gait speed using the Midlife in the United States (MIDUS) study biomarker dataset. A cross-sectional design was employed for analysis, involving 405 individuals aged 60 years and over. We used a machine learning framework, specifically the XGBoost algorithm, feature selection methods, and the Shapley Additive Explanations, to develop an explainable prediction model for slow gait speed. Our model demonstrated the highest cross-validation score with the six most important features among 35 variables, as elevated interleukin-6, C-reactive protein, glycosylated hemoglobin, interleukin-8, older age, and female sex were significantly associated with reduced gait speed (area under the curve = 0.75). Our findings suggest that blood biomarkers can play a critical role in integrated models to assess and monitor slow gait speed in older adults. Identifying key blood biomarkers provides valuable insights into the underlying physiological mechanisms of mobility decline and offers promising avenues for early intervention to preserve mobility in the aging population.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 295-304"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823598","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}
Feather pecking (FP) is a serious behavioral disorder in laying hens, leading to feather damage, skin lesions, and often resulting in cannibalism. The mechanisms underlying FP are not clear yet, but recently the role of the immune system as a cause has been discussed. In humans, the interrelation between personality traits and the immune system is well-documented, with impulsivity and hyperactivity linked to distinct alterations in blood immune cell numbers and to elevated levels of pro-inflammatory cytokines. Similarly, FP in hens is associated with impulsivity and hyperactivity, suggesting a possible connection between FP and immune cell alterations. In this study numbers of leukocyte subsets in blood, spleen and cecal tonsils, along with mitogen-induced lymphocyte proliferative response and antibody concentrations across hens selectively bred for high (HFP) and low (LFP) feather pecking behavior were analyzed. Results showed that divergent selection altered FP behavior, with HFP hens showing about 10 times more pecking behavior than hens of the LFP line. HFP hens had lower numbers of T helper cells, CD4+ CD25high as well as B cells compared to LFP hens. Furthermore, HFP hens demonstrated a stronger proliferation of T cells when stimulated with ConA, while showed a weaker response in T cell-dependent B cell proliferation when stimulated with PWM, compared to LFP hens. Antibody plasma concentrations were similar between both lines. These findings highlight substantial immunological differences between HFP and LFP hens, especially in T cell immunity, and support the hypothesis that FP may be an immune-related behavioral response.
啄羽（FP）是蛋鸡的一种严重行为紊乱，会导致羽毛损伤、皮肤损伤，并经常导致食人。啄羽症的发病机制尚不清楚，但最近有人讨论了免疫系统的作用。在人类中，个性特征与免疫系统之间的相互关系已得到充分证明，冲动和多动与血液免疫细胞数量的明显变化和促炎细胞因子水平的升高有关。同样，母鸡的FP也与冲动和多动有关，这表明FP与免疫细胞的改变之间可能存在联系。本研究分析了高啄羽行为（HFP）和低啄羽行为（LFP）选育母鸡血液、脾脏和盲肠扁桃体中白细胞亚群的数量，以及有丝分裂原诱导的淋巴细胞增殖反应和抗体浓度。结果表明，分化选择改变了啄羽行为，高啄羽系母鸡的啄羽行为是低啄羽系母鸡的约10倍。与 LFP 母鸡相比，HFP 母鸡的 T 辅助细胞、CD4+ CD25high 和 B 细胞数量较低。此外，与 LFP 系母鸡相比，HFP 系母鸡在接受 ConA 刺激时 T 细胞增殖较强，而在接受 PWM 刺激时 T 细胞依赖性 B 细胞增殖反应较弱。两个品系的抗体血浆浓度相似。这些发现突显了HFP和LFP母鸡在免疫学上的巨大差异，尤其是在T细胞免疫方面，并支持了FP可能是一种与免疫相关的行为反应的假设。
{"title":"From feather pecking to immunity: Immune differences between lines selected for high and low feather pecking","authors":"Tanja Hofmann , Sonja Schmucker , Werner Bessei , Volker Stefanski","doi":"10.1016/j.bbi.2024.12.009","DOIUrl":"10.1016/j.bbi.2024.12.009","url":null,"abstract":"<div><div>Feather pecking (FP) is a serious behavioral disorder in laying hens, leading to feather damage, skin lesions, and often resulting in cannibalism. The mechanisms underlying FP are not clear yet, but recently the role of the immune system as a cause has been discussed. In humans, the interrelation between personality traits and the immune system is well-documented, with impulsivity and hyperactivity linked to distinct alterations in blood immune cell numbers and to elevated levels of pro-inflammatory cytokines. Similarly, FP in hens is associated with impulsivity and hyperactivity, suggesting a possible connection between FP and immune cell alterations. In this study numbers of leukocyte subsets in blood, spleen and cecal tonsils, along with mitogen-induced lymphocyte proliferative response and antibody concentrations across hens selectively bred for high (HFP) and low (LFP) feather pecking behavior were analyzed. Results showed that divergent selection altered FP behavior, with HFP hens showing about 10 times more pecking behavior than hens of the LFP line. HFP hens had lower numbers of T helper cells, CD4+ CD25<sup>high</sup> as well as B cells compared to LFP hens. Furthermore, HFP hens demonstrated a stronger proliferation of T cells when stimulated with ConA, while showed a weaker response in T cell-dependent B cell proliferation when stimulated with PWM, compared to LFP hens. Antibody plasma concentrations were similar between both lines. These findings highlight substantial immunological differences between HFP and LFP hens, especially in T cell immunity, and support the hypothesis that FP may be an immune-related behavioral response.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 253-263"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823646","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}
Pub Date : 2025-02-01DOI: 10.1016/S0889-1591(25)00009-1
{"title":"PNIRS Society Announcements","authors":"","doi":"10.1016/S0889-1591(25)00009-1","DOIUrl":"10.1016/S0889-1591(25)00009-1","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages iv-v"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094703","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}
Pub Date : 2025-02-01DOI: 10.1016/j.bbi.2024.11.027
Courtney N. Dye , Aliyah I. Webb , Madison P. Fankhauser , Jordyn J. Singleton , Aravind Kalathil , Amanda Ringland , Benedetta Leuner , Kathryn M. Lenz
7 % of pregnant people use opioids. Opioid use during pregnancy can negatively impact maternal and offspring health. Medications for opioid use disorder (MOUD), commonly buprenorphine, are the recommended treatment for opioid use disorder during pregnancy to prevent cycles of withdrawal and relapse. In addition to effects on opioid receptors, opioids have strong binding affinity to toll-like receptor (TLR) 4, an immune cell receptor, and thereby impact neuroinflammatory signaling. We have previously shown that neuroimmune alterations are important for the display of maternal behavior. Here, we used a rodent model to assess the impact of chronic peripartum opioid exposure or MOUD on maternal caregiving and neuroinflammation in the postpartum brain. Female rats were exposed to vehicle (VEH), buprenorphine (BUP) to model MOUD, or oxycodone (OXY), to model peripartum drug use, before, during, and after pregnancy. Opioid exposure reduced gestation length and maternal weight gain. Postpartum maternal caretaking behaviors, including pup retrieval, huddling and nursing, and pup-directed sniffing and licking, were reduced in opioid-exposed mothers. Following behavioral testing, tissue was collected from brain regions important for maternal caretaking, including the prefrontal cortex (PFC), nucleus accumbens (NAc), preoptic area (POA), amygdala (AMY), and periaqueductal grey (PAG). Immunofluorescent labeling showed that BUP increased astrocyte labeling, while OXY increased microglia labeling in the PAG, but not other regions. Gene expression analysis also showed regional and treatment differences in immune transcripts. BUP and OXY increased TLR4 in the PFC. BUP increased TNF in the NAc but decreased IL1β in the POA. OXY increased CD68 in the POA, and IL1β, TNF, and TLR4 in the PAG. Together, these results provide novel evidence of peripartum neuroimmune alterations following chronic opioid exposure that could be mediating maternal care deficits. This work provides a foundation to explore the extent to which modulation of neuroimmune activation may be a potential intervention for caregiving deficits in mothers exposed to opioids during pregnancy.
{"title":"Peripartum buprenorphine and oxycodone exposure impair maternal behavior and increase neuroinflammation in new mother rats","authors":"Courtney N. Dye , Aliyah I. Webb , Madison P. Fankhauser , Jordyn J. Singleton , Aravind Kalathil , Amanda Ringland , Benedetta Leuner , Kathryn M. Lenz","doi":"10.1016/j.bbi.2024.11.027","DOIUrl":"10.1016/j.bbi.2024.11.027","url":null,"abstract":"<div><div>7 % of pregnant people use opioids. Opioid use during pregnancy can negatively impact maternal and offspring health. Medications for opioid use disorder (MOUD), commonly buprenorphine, are the recommended treatment for opioid use disorder during pregnancy to prevent cycles of withdrawal and relapse. In addition to effects on opioid receptors, opioids have strong binding affinity to toll-like receptor (TLR) 4, an immune cell receptor, and thereby impact neuroinflammatory signaling. We have previously shown that neuroimmune alterations are important for the display of maternal behavior. Here, we used a rodent model to assess the impact of chronic peripartum opioid exposure or MOUD on maternal caregiving and neuroinflammation in the postpartum brain. Female rats were exposed to vehicle (VEH), buprenorphine (BUP) to model MOUD, or oxycodone (OXY), to model peripartum drug use, before, during, and after pregnancy. Opioid exposure reduced gestation length and maternal weight gain. Postpartum maternal caretaking behaviors, including pup retrieval, huddling and nursing, and pup-directed sniffing and licking, were reduced in opioid-exposed mothers. Following behavioral testing, tissue was collected from brain regions important for maternal caretaking, including the prefrontal cortex (PFC), nucleus accumbens (NAc), preoptic area (POA), amygdala (AMY), and periaqueductal grey (PAG). Immunofluorescent labeling showed that BUP increased astrocyte labeling, while OXY increased microglia labeling in the PAG, but not other regions. Gene expression analysis also showed regional and treatment differences in immune transcripts. BUP and OXY increased TLR4 in the PFC. BUP increased TNF in the NAc but decreased IL1β in the POA. OXY increased CD68 in the POA, and IL1β, TNF, and TLR4 in the PAG. Together, these results provide novel evidence of peripartum neuroimmune alterations following chronic opioid exposure that could be mediating maternal care deficits. This work provides a foundation to explore the extent to which modulation of neuroimmune activation may be a potential intervention for caregiving deficits in mothers exposed to opioids during pregnancy.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 264-279"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754681","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}
Pub Date : 2025-02-01DOI: 10.1016/j.bbi.2024.12.015
Xicai Liang , Gege Li , Ziyin Cui , Jing Chen
{"title":"Commentary on the Article “Female mice exhibit similar long-term plasticity and microglial properties between the dorsal and ventral hippocampal poles”","authors":"Xicai Liang , Gege Li , Ziyin Cui , Jing Chen","doi":"10.1016/j.bbi.2024.12.015","DOIUrl":"10.1016/j.bbi.2024.12.015","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 385-386"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823611","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}
Pub Date : 2025-02-01DOI: 10.1016/j.bbi.2024.12.005
Keren Harel , Johanna Czamanski-Cohen , Miri Cohen , Richard D. Lane , Monica Dines , Opher Caspi , Karen L. Weihs
Cancer survivors have elevated levels of proinflammatory cytokines, which could be associated with cancer-related symptoms. Given that proinflammatory cytokines heighten negative affect by directly affecting the brain, we explored these direct associations and whether differences in levels of emotional awareness moderate the associations between proinflammatory cytokines and cancer-related symptoms. This cross-sectional, secondary analysis of baseline data was collected from 162 female breast cancer survivors (aged 36–70 years), who were enrolled 6 ± 4 months after completing cancer treatment. We tested cytokines in serum (IL-1β, IL-6, IL-8, TNF-α, IL-4, IL-10, and TGF-β) and assessed depression, cancer-related fatigue, pain intensity, and pain interference. Emotional awareness was assessed using a performance measure, the Levels of Emotional Awareness Scale. In participants with high but not average or low levels of emotional awareness, positive associations were found for IL-1β, IL-6, and TNF-α with depression and between IL-6 and TNF-α with pain intensity. In addition, IL-6 had a positive association with pain intensity at average levels of emotional awareness. These results suggest that women with high or in some cases average, but not low, emotional awareness reported depression and pain as being positively associated with their cytokine levels. By using emotional awareness as a cognitive resource to promote emotion regulation and distress transformation, interventions may be able to counteract heightened sensitivity to the mood-altering effects of cytokines.
{"title":"Differences in Emotional Awareness Moderate Cytokine-Symptom Associations Among Breast Cancer Survivors","authors":"Keren Harel , Johanna Czamanski-Cohen , Miri Cohen , Richard D. Lane , Monica Dines , Opher Caspi , Karen L. Weihs","doi":"10.1016/j.bbi.2024.12.005","DOIUrl":"10.1016/j.bbi.2024.12.005","url":null,"abstract":"<div><div>Cancer survivors have elevated levels of proinflammatory cytokines, which could be associated with cancer-related symptoms. Given that proinflammatory cytokines heighten negative affect by directly affecting the brain, we explored these direct associations and whether differences in levels of emotional awareness moderate the associations between proinflammatory cytokines and cancer-related symptoms. This cross-sectional, secondary analysis of baseline data was collected from 162 female breast cancer survivors (aged 36–70 years), who were enrolled 6 ± 4 months after completing cancer treatment. We tested cytokines in serum (IL-1β, IL-6, IL-8, TNF-α, IL-4, IL-10, and TGF-β) and assessed depression, cancer-related fatigue, pain intensity, and pain interference. Emotional awareness was assessed using a performance measure, the Levels of Emotional Awareness Scale. In participants with high but not average or low levels of emotional awareness, positive associations were found for IL-1β, IL-6, and TNF-α with depression and between IL-6 and TNF-α with pain intensity. In addition, IL-6 had a positive association with pain intensity at average levels of emotional awareness. These results suggest that women with high or in some cases average, but not low, emotional awareness reported depression and pain as being positively associated with their cytokine levels. By using emotional awareness as a cognitive resource to promote emotion regulation and distress transformation, interventions may be able to counteract heightened sensitivity to the mood-altering effects of cytokines.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 387-396"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823624","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}
Pub Date : 2025-02-01DOI: 10.1016/j.bbi.2024.12.017
Sebastian Proschinger , Sergen Belen , Frederike Adammek , Marit Lea Schlagheck , Annette Rademacher , Alexander Schenk , Clemens Warnke , Wilhelm Bloch , Philipp Zimmer
Background
Multiple Sclerosis (MS) represents a neuroinflammatory autoimmune disease characterized by the predominance of circulating T cell subsets with proinflammatory characteristics and increased central nervous system (CNS)-homing potential. Substantial evidence confirms various beneficial effects of chronic exercise interventions in MS, but it is unknown how long-term multi-modal intense exercise affects MS-associated lymphocytes that are commonly targeted by medication in persons with relapsing remitting MS (pwRRMS).
Methods
A total of 45 participants with defined RRMS were randomized to either the exercise (n = 22) or passive waitlist-control group (n = 23). A 10-week intervention consisting of progressive resistance and strength-endurance exercises was applied (3x/week à 60 min). Blood was drawn before (T1) and after (T2) the intervention period. Flow cytometry was used for phenotyping lymphocyte subsets.
Results
Relative protein expression of CD49d within CD8+ T cells, quantified via mean fluorescence intensity (MFI), is significantly associated with the Expanded Disability Status Scale (p = 0.007, r = 0.440), decreased in the exercise group (p = 0.001) only, and was significantly lower in the exercise compared to the control group at T2 (p < 0.001). T helper (Th) 17 cell frequency decreased only in the exercise group (p < 0.001). CD8+CD20+ T cell frequency was significantly lower in the exercise compared to the control group at T2 (p = 0.003), without showing significant time effects.
Conclusion
The 10-week multimodal exercise intervention mainly affected circulating T cells harboring a pathophysiological phenotype in MS. The findings of a decreased frequency of pathogenic Th17 cells and the reduced CNS-homing potential of CD8+ T cells, indicated by reduced CD49d MFI, substantiate the positive effects of exercise on cellular biomarkers involved in disease activity and progression in MS. To confirm exercise-mediated beneficial effects on both disease domains, clinical endpoints (i.e., relapse rate, lesion formation, EDSS score) should be assessed together with these cellular and molecular markers in studies with a larger sample size and a duration of six to twelve months or longer.
{"title":"Sportizumab – Multimodal progressive exercise over 10 weeks decreases Th17 frequency and CD49d expression on CD8+ T cells in relapsing-remitting multiple sclerosis: A randomized controlled trial","authors":"Sebastian Proschinger , Sergen Belen , Frederike Adammek , Marit Lea Schlagheck , Annette Rademacher , Alexander Schenk , Clemens Warnke , Wilhelm Bloch , Philipp Zimmer","doi":"10.1016/j.bbi.2024.12.017","DOIUrl":"10.1016/j.bbi.2024.12.017","url":null,"abstract":"<div><h3>Background</h3><div>Multiple Sclerosis (MS) represents a neuroinflammatory autoimmune disease characterized by the predominance of circulating T cell subsets with proinflammatory characteristics and increased central nervous system (CNS)-homing potential. Substantial evidence confirms various beneficial effects of chronic exercise interventions in MS, but it is unknown how long-term multi-modal intense exercise affects MS-associated lymphocytes that are commonly targeted by medication in persons with relapsing remitting MS (pwRRMS).</div></div><div><h3>Methods</h3><div>A total of 45 participants with defined RRMS were randomized to either the exercise (n = 22) or passive waitlist-control group (n = 23). A 10-week intervention consisting of progressive resistance and strength-endurance exercises was applied (3x/week à 60 min). Blood was drawn before (T<sub>1</sub>) and after (T<sub>2</sub>) the intervention period. Flow cytometry was used for phenotyping lymphocyte subsets.</div></div><div><h3>Results</h3><div>Relative protein expression of CD49d within CD8<sup>+</sup> T cells, quantified via mean fluorescence intensity (MFI), is significantly associated with the Expanded Disability Status Scale (p = 0.007, r = 0.440), decreased in the exercise group (p = 0.001) only, and was significantly lower in the exercise compared to the control group at T<sub>2</sub> (p < 0.001). T helper (Th) 17 cell frequency decreased only in the exercise group (p < 0.001). CD8<sup>+</sup>CD20<sup>+</sup> T cell frequency was significantly lower in the exercise compared to the control group at T<sub>2</sub> (p = 0.003), without showing significant time effects.</div></div><div><h3>Conclusion</h3><div>The 10-week multimodal exercise intervention mainly affected circulating T cells harboring a pathophysiological phenotype in MS. The findings of a decreased frequency of pathogenic Th17 cells and the reduced CNS-homing potential of CD8<sup>+</sup> T cells, indicated by reduced CD49d MFI, substantiate the positive effects of exercise on cellular biomarkers involved in disease activity and progression in MS. To confirm exercise-mediated beneficial effects on both disease domains, clinical endpoints (i.e., relapse rate, lesion formation, EDSS score) should be assessed together with these cellular and molecular markers in studies with a larger sample size and a duration of six to twelve months or longer.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 397-408"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827334","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}
Pub Date : 2025-02-01DOI: 10.1016/j.bbi.2024.11.015
Josh Karam , Nimrah Ashfaq , Cynthia Benitez , Victor Morales , Elizabeth Partida , Michelle Hernandez , Jordan Yokoyama , Alyssa Villegas , Brielle Brown , Pooja Sakthivel , Aileen J. Anderson , Brian J. Cummings
Traumatic brain injuries (TBI) are the seventh leading cause of disability globally with 48.99 million prevalent cases and 7.08 million years lived with diability. Approximately 80 % of TBI patients are diagnosed with mild TBI (mTBI), or concussion, caused by nonpenetrating mechanical trauma to the head or body along with sudden rotational motion of the head. Studies investigating the temporal dynamics of neuroinflammation after mTBI are greatly needed. Without longitudinal studies, translating preclinical studies to clinical studies remains challenging as the difference in timing remains poorly understood. In this study, we describe a method of minimally invasive serial cerebrospinal fluid (CSF) collection that enables longitudinal investigation of CSF inflammation. The method described in this study can easily be adapted by any laboratory prepared for animal studies. Multiplex immunoassay of serially collected and singly collected CSF samples show collection frequency does not alter protein expression in the CSF. Further, sex-dependent differences in TBI have been reported, but remain poorly understood. This study establishes a framework for assessing sex difference in neuroinflammation after a concussion. We showed that results vary based on the framing of the statistical test. However, it is evident that males experience a more robust inflammatory response to a single concussion than females.
{"title":"Minimally invasive serial collection of cerebrospinal fluid reveals sex-dependent differences in neuroinflammation in a rat model of mild traumatic brain injury","authors":"Josh Karam , Nimrah Ashfaq , Cynthia Benitez , Victor Morales , Elizabeth Partida , Michelle Hernandez , Jordan Yokoyama , Alyssa Villegas , Brielle Brown , Pooja Sakthivel , Aileen J. Anderson , Brian J. Cummings","doi":"10.1016/j.bbi.2024.11.015","DOIUrl":"10.1016/j.bbi.2024.11.015","url":null,"abstract":"<div><div>Traumatic brain injuries (TBI) are the seventh leading cause of disability globally with 48.99 million prevalent cases and 7.08 million years lived with diability. Approximately 80 % of TBI patients are diagnosed with mild TBI (mTBI), or concussion, caused by nonpenetrating mechanical trauma to the head or body along with sudden rotational motion of the head. Studies investigating the temporal dynamics of neuroinflammation after mTBI are greatly needed. Without longitudinal studies, translating preclinical studies to clinical studies remains challenging as the difference in timing remains poorly understood. In this study, we describe a method of minimally invasive serial cerebrospinal fluid (CSF) collection that enables longitudinal investigation of CSF inflammation. The method described in this study can easily be adapted by any laboratory prepared for animal studies. Multiplex immunoassay of serially collected and singly collected CSF samples show collection frequency does not alter protein expression in the CSF. Further, sex-dependent differences in TBI have been reported, but remain poorly understood. This study establishes a framework for assessing sex difference in neuroinflammation after a concussion. We showed that results vary based on the framing of the statistical test. However, it is evident that males experience a more robust inflammatory response to a single concussion than females.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 237-252"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754680","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}
Pub Date : 2025-02-01DOI: 10.1016/j.bbi.2024.12.018
Wenhui Liu , Kai Yan , Siqi Xu , Lifang Li , Mengdan Zhong , Jing Liu , Guoying Li , Junhua Yang
Prenatal virus infection-induced maternal immune activation (MIA) is linked to a greater risk of neurodevelopmental disorders in offspring. Prenatal exposure to poly(I:C) in pregnant mice is a well-established approach to mimic virus infection-induced MIA, leading to neuropsychiatric disorders and aberrant brain development, especially in the medial prefrontal cortex (mPFC). ATPase phospholipid flippase 8A2 (ATP8A2) is the main phospholipid lipase, expressed in the mPFC and is crucial for maintaining cell membrane stability by flipping phosphatidylserine from the outer leaflet to the inner leaflet of the cell membrane. Atp8a2 knockout or mutation causes a series of phenotypes, including impaired neuronal cell survival, neuroinflammation, altered synaptic plasticity, and behavioral abnormalities. These findings suggest that ATP8A2 expression in the mPFC may be impaired in MIA offspring and that the decrease in ATP8A2 expression may be involved in the development of MIA-induced neuropsychiatric disorders in offspring. No reports addressing this issue have been published. Here, after confirming abnormal affective-/social-related behaviors in adulthood and reduced synapse-associated protein expression on the birth day (P0) and the fourth postnatal day (P4) in the mPFC of MIA offspring that were born to dams exposed prenatally to a single dose of poly(I:C) (10 mg/kg, i.p.), decreased ATP8A2 expression was also observed in the mPFC of MIA offspring at P0 and P4. Upregulating ATP8A2 in the mPFC restored synapse-associated protein levels, along with a partial improvement in the behavioral performance of MIA offspring. Upregulation of ATP8A2 also blocked neuronal phosphatidylserine externalization and eliminated the excitation/inhibition (E/I) imbalance in the mPFC of MIA offspring. This study revealed that the low expression of ATP8A2 following MIA exposure may play a role in mediating abnormal brain development and function in offspring. ATP8A2 potentially represents a novel molecule involved in MIA-induced neuropsychiatric disorders in offspring, and may serve as a novel therapeutic target for the intervention of psychiatric disorders.
{"title":"ATP8A2 expression is reduced in the mPFC of offspring mice exposed to maternal immune activation and its upregulation ameliorates synapse-associated protein loss and behavioral abnormalities","authors":"Wenhui Liu , Kai Yan , Siqi Xu , Lifang Li , Mengdan Zhong , Jing Liu , Guoying Li , Junhua Yang","doi":"10.1016/j.bbi.2024.12.018","DOIUrl":"10.1016/j.bbi.2024.12.018","url":null,"abstract":"<div><div>Prenatal virus infection-induced maternal immune activation (MIA) is linked to a greater risk of neurodevelopmental disorders in offspring. Prenatal exposure to poly(I:C) in pregnant mice is a well-established approach to mimic virus infection-induced MIA, leading to neuropsychiatric disorders and aberrant brain development, especially in the medial prefrontal cortex (mPFC). ATPase phospholipid flippase 8A2 (ATP8A2) is the main phospholipid lipase, expressed in the mPFC and is crucial for maintaining cell membrane stability by flipping phosphatidylserine from the outer leaflet to the inner leaflet of the cell membrane. <em>Atp8a2</em> knockout or mutation causes a series of phenotypes, including impaired neuronal cell survival, neuroinflammation, altered synaptic plasticity, and behavioral abnormalities. These findings suggest that ATP8A2 expression in the mPFC may be impaired in MIA offspring and that the decrease in ATP8A2 expression may be involved in the development of MIA-induced neuropsychiatric disorders in offspring. No reports addressing this issue have been published. Here, after confirming abnormal affective-/social-related behaviors in adulthood and reduced synapse-associated protein expression on the birth day (P0) and the fourth postnatal day (P4) in the mPFC of MIA offspring that were born to dams exposed prenatally to a single dose of poly(I:C) (10 mg/kg, i.p.), decreased ATP8A2 expression was also observed in the mPFC of MIA offspring at P0 and P4.<!--> <!-->Upregulating ATP8A2 in the mPFC restored synapse-associated protein levels, along with a partial improvement in the behavioral performance of MIA offspring. Upregulation of ATP8A2 also blocked neuronal phosphatidylserine externalization and eliminated the excitation/inhibition (E/I) imbalance in the mPFC of MIA offspring. This study revealed that the low expression of ATP8A2 following MIA exposure may play a role in mediating abnormal brain development and function in offspring. ATP8A2 potentially represents a novel molecule involved in MIA-induced neuropsychiatric disorders in offspring, and may serve as a novel therapeutic target for the intervention of psychiatric disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 409-430"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833716","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}
Pub Date : 2025-02-01DOI: 10.1016/j.bbi.2024.11.030
Attila Szabo , Ibrahim Akkouh , Jordi Requena Osete , Denis Reis de Assis , Elena Kondratskaya , Timothy Hughes , Thor Ueland , Ole A. Andreassen , Srdjan Djurovic
Mounting evidence indicates the involvement of neuroinflammation in the development of schizophrenia (SCZ), but the potential role of astroglia in this phenomenon remains poorly understood. We assessed the molecular and functional consequences of inflammasome activation using induced pluripotent stem cell (iPSC)-derived astrocytes generated from SCZ patients and healthy controls (CTRL). Screening protein levels in astrocytes at baseline identified lower expression of the NLRP3-ASC complex in SCZ, but increased Caspase-1 activity upon specific NLRP3 stimulation compared to CTRL. Using transcriptional profiling, we found corresponding downregulations of NLRP3 and ASC/PYCARD in both iPSC-derived astrocytes, and in a large (n = 429) brain postmortem case-control sample. Functional analyses following NLRP3 activation revealed an inflammatory phenotype characterized by elevated production of IL-1β/IL-18 and skewed priming of helper T lymphocytes (Th1/Th17) by SCZ astrocytes. This phenotype was rescued by specific inhibition of NLRP3 activation, demonstrating its dependence on the NLRP3 inflammasome. Taken together, SCZ iPSC-astrocytes display unique, NLRP3-dependent inflammatory characteristics that are manifested via various cellular functions, as well as via dysregulated innate and adaptive immune responses.
{"title":"NLRP3 inflammasome mediates astroglial dysregulation of innate and adaptive immune responses in schizophrenia","authors":"Attila Szabo , Ibrahim Akkouh , Jordi Requena Osete , Denis Reis de Assis , Elena Kondratskaya , Timothy Hughes , Thor Ueland , Ole A. Andreassen , Srdjan Djurovic","doi":"10.1016/j.bbi.2024.11.030","DOIUrl":"10.1016/j.bbi.2024.11.030","url":null,"abstract":"<div><div>Mounting evidence indicates the involvement of neuroinflammation in the development of schizophrenia (SCZ), but the potential role of astroglia in this phenomenon remains poorly understood. We assessed the molecular and functional consequences of inflammasome activation using induced pluripotent stem cell (iPSC)-derived astrocytes generated from SCZ patients and healthy controls (CTRL). Screening protein levels in astrocytes at baseline identified lower expression of the NLRP3-ASC complex in SCZ, but increased Caspase-1 activity upon specific NLRP3 stimulation compared to CTRL. Using transcriptional profiling, we found corresponding downregulations of <em>NLRP3</em> and <em>ASC/PYCARD</em> in both iPSC-derived astrocytes, and in a large (n = 429) brain postmortem case-control sample. Functional analyses following NLRP3 activation revealed an inflammatory phenotype characterized by elevated production of IL-1β/IL-18 and skewed priming of helper T lymphocytes (Th1/Th17) by SCZ astrocytes. This phenotype was rescued by specific inhibition of NLRP3 activation, demonstrating its dependence on the NLRP3 inflammasome. Taken together, SCZ iPSC-astrocytes display unique, NLRP3-dependent inflammatory characteristics that are manifested via various cellular functions, as well as via dysregulated innate and adaptive immune responses.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 144-156"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766326","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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