Brain, Behavior, and Immunity最新文献

{"title":"mAbsolutely FABulous: From a case of mistaken identity to pinpoint precision in the antibodies formerly known as ‘VGKC’","authors":"Sophie N.M. Binks","doi":"10.1016/j.bbi.2024.10.040","DOIUrl":"10.1016/j.bbi.2024.10.040","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 838-839"},"PeriodicalIF":8.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543763","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":"Running therapy or antidepressants as treatments for immunometabolic depression in patients with depressive and anxiety disorders: A secondary analysis of the MOTAR study","authors":"Sarah R. Vreijling ,&nbsp;Brenda W.J.H. Penninx ,&nbsp;Josine E. Verhoeven ,&nbsp;Charlotte E. Teunissen ,&nbsp;Elena R. Blujdea ,&nbsp;Aartjan T.F. Beekman ,&nbsp;Femke Lamers ,&nbsp;Rick Jansen","doi":"10.1016/j.bbi.2024.10.033","DOIUrl":"10.1016/j.bbi.2024.10.033","url":null,"abstract":"<div><h3>Background</h3><div>Exercise promotes immunometabolic health and is increasingly recognized as an effective depression treatment. Exercise may be beneficial for patients with immunometabolic depression (IMD), who experience inflammatory and metabolic dysregulations and may respond less to antidepressants. This secondary analysis of the MOTAR study compared the effects of running therapy and antidepressants on IMD features among patients with depression and/or anxiety disorder. We additionally assessed whether baseline IMD moderated intervention effects on depression.</div></div><div><h3>Methods</h3><div>Participants received 16 weeks of group-based running therapy (N = 96) or escitalopram/sertraline (N = 45) in a partially randomized patient preference design. IMD features included atypical, energy-related symptom (AES) severity, inflammation index (CRP, IFN-γ, IL-6, TNF-α), metabolic syndrome index, three metabolite principle components (PC) (derived from 73 metabolites) and a composite IMD index.</div></div><div><h3>Results</h3><div>Interventions differed in changes in the metabolic syndrome index (d = 0.59, p = 0.026) and IMD index (d = 0.85, p &lt; 0.001). While running therapy decreased both outcomes, the antidepressant group showed an increased IMD index. Although groups did not differ statistically significant in changes in AES severity, inflammation index, and metabolite PC1, results indicated a consistent trend towards greater improvement with running therapy across these outcomes as well (d = 0.38 to 0.52). Baseline IMD did not moderate intervention effects on depression outcomes.</div></div><div><h3>Conclusions</h3><div>This study suggests that exercise more effectively targets the IMD dimension than antidepressants. Patients with IMD did not benefit more from running therapy than antidepressants in terms of reductions in depression. Exercise should be considered an alternative or complementary treatment to particularly reduce IMD features in depressed patients.</div></div><div><h3>Trial registration</h3><div><span><span>Trialregister.nl</span><svg><path></path></svg></span> Number of identification: NTR3460.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 876-883"},"PeriodicalIF":8.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543764","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":"Gut microbiota transfer from the preclinical maternal immune activation model of autism is sufficient to induce sex-specific alterations in immune response and behavioural outcomes","authors":"Stephanie Salia,&nbsp;Francine F. Burke,&nbsp;Meagan E. Hinks,&nbsp;Alison M. Randell,&nbsp;Mairead Anna Matheson,&nbsp;Susan G. Walling,&nbsp;Ashlyn Swift-Gallant","doi":"10.1016/j.bbi.2024.10.030","DOIUrl":"10.1016/j.bbi.2024.10.030","url":null,"abstract":"<div><div>The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., <em>Lactobacillus</em> and <em>Rikenella</em>). These results suggest that gut reactivity to environmental insults, such as in the MIA model, may play a role in shaping the sex disparity in ASD development.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 813-823"},"PeriodicalIF":8.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543765","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":"Bidirectional interaction between IL and 17A/IL-17RA pathway dysregulation and α-synuclein in the pathogenesis of Parkinson's disease.","authors":"Yu-Chen Yan, Lu Su, Wan-Bing Zhao, Yun Fan, James B Koprich, Bao-Guo Xiao, Bin Song, Jian Wang, Wen-Bo Yu","doi":"10.1016/j.bbi.2024.10.025","DOIUrl":"https://doi.org/10.1016/j.bbi.2024.10.025","url":null,"abstract":"<p><p>Parkinson's disease (PD) pathogenesis is characterized by α-synuclein (α-syn) pathology, which is influenced by various factors such as neuroinflammation and senescence. Increasing evidence has suggested a pivotal role for Interleukin-17A(IL-17A) and Interleukin-17 Receptor A (IL-17RA) in PD, yet the trigger and impact of IL-17A/IL-17RA activation in PD remains elusive. This study observed an age-related increase in IL-17A and IL-17RA in the human central nervous system, accompanied by increased α-syn and senescence biomarkers. Interestingly, both levels of IL-17A and IL-17RA in PD patients were significantly elevated compared to age-matched controls, wherein the IL-17A was mainly present in neurons. This abnormal neuronal IL-17A activation in the PD brain was recapitulated in α-syn mouse models. Correspondingly, administration of recombinant IL-17A exacerbated pathological α-syn in both neuron and mouse models. Furthermore, IL-17A/IL-17RA pathway interventions via blocking antibody or shRNA-mediated knockdown can mitigate the effects of pathological α-syn. This study reveals an interplay between dysregulation of the IL-17A/IL-17RA pathway and α-syn, suggesting that regulating the IL-17A/IL-17RA pathway could modify PD progression by disrupting the detrimental cycle.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495344","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":"Chemogenetic targeting TRPV1 in obesity-induced depression: Unveiling therapeutic potential of eicosapentaenoic acid and acupuncture","authors":"Yi-Wen Lin ,&nbsp;Szu-Wei Cheng ,&nbsp;Wen-Chun Liu ,&nbsp;Halliru Zailani ,&nbsp;Suet-Kei Wu ,&nbsp;Mien-Chie Hung ,&nbsp;Kuan-Pin Su","doi":"10.1016/j.bbi.2024.10.028","DOIUrl":"10.1016/j.bbi.2024.10.028","url":null,"abstract":"<div><div>The comorbidity of obesity and depression has major public health impacts, highlighting the need to understand their shared mechanisms. This study explored the connection between obesity and depression through the transient receptor potential V1 (TRPV1) signaling pathway, using obese/depressed murine models and clinical data. Mice fed a high-fat diet showed altered TRPV1 pathway expression in brain regions of the mice: downregulated in the medial prefrontal cortex (mPFC) and hippocampus, and upregulated in the hypothalamus and amygdala, influencing depression-like behaviors and inflammation. Treatments like eicosapentaenoic acid (EPA) and acupoint catgut embedding (ACE) reversed these effects, similar to observations in Trpv1^−/− mice. Furthermore, chemogenetic activation in the ventral mPFC also alleviated depression via TRPV1. In our clinical validation, single nucleotide polymorphisms (SNPs) in TRPV1-related genes (PIK3C2A and PRKCA) were linked to interferon-induced depression. These findings underscore the potential of targeting TRPV1 as a therapeutic approach for obesity-related depression.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 771-783"},"PeriodicalIF":8.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495345","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":"Peptidoglycan accumulates in distinct brain regions and cell types over lifetime but is absent in newborns","authors":"Carolin Zeiher ,&nbsp;Heidrun Kuhrt ,&nbsp;Aline Rifflet ,&nbsp;Karsten Winter ,&nbsp;Louis Boon ,&nbsp;Ruth M. Stassart ,&nbsp;Erik Nutma ,&nbsp;Jinte Middeldorp ,&nbsp;Inge M. Strating ,&nbsp;Ivo G. Boneca ,&nbsp;Ingo Bechmann ,&nbsp;Jon D. Laman","doi":"10.1016/j.bbi.2024.10.024","DOIUrl":"10.1016/j.bbi.2024.10.024","url":null,"abstract":"<div><div>Peptidoglycan (PGN) is a large complex polymer critical to structure and function of all bacterial species. Intact PGN and its fragments are inflammatory, contributing to infectious and autoimmune disease. Recent studies show that PGN physiologically contributes to immune setpoints, and importantly also to mouse brain development and behavior. However, for the human brain, it remains unknown whether PGN and its fragments differentially gain access to distinct brain regions, which cell types accumulate it, and whether PGN brain load varies with age. Therefore, we investigated human postmortem brain samples of donors with an extensive age range, from newborns to nonagenarians. We examined two monoclonal antibodies against PGN which were validated using dot blot analysis, competition assays and immunofluorescence experiments on bacteria sacculi, which jointly showed specific detection of Gram-positive PGN. As positive reference tissue, brain tissue from sepsis patients, and human liver were used, both showing the expected high PGN levels. In adult brain tissue of different age (34- to 94-year-old) and sex, we detected PGN signals in seven different brain regions, with highest loads in the occipital cortex, hippocampal formation, frontal cortex, the periventricular region and the olfactory bulb. Age-dependent increase of signals was not evident by microscopic observations and only weak correlation was found by statistical analysis in this cohort. PGN was found intracellularly in the cytoplasm surrounding the cell nucleus in astrocytes, oligodendrocytes, neurons, and endothelial cells, but not in macrophages like microglia. PGN was absent in brain tissues of three human newborns (stillbirth to four weeks old). For comparison, three brain regions from non-human primates of varying age (newborn to 21 years) were immunohistochemically stained. The highest PGN-load was observed in brain tissue from 18- to 21-year-old macaques.</div><div>This first systematic evaluation of PGN in human postmortem brain suggests that PGN accumulates during lifetime until it reaches a plateau by homeostatic turnover and highlights the ubiquitous presence of PGN in human brain tissues, and their ability to participate in physiological as well as pathological processes throughout life.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 799-812"},"PeriodicalIF":8.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495348","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":"C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model of prematurity","authors":"Cécile Morin ,&nbsp;Flora Faure ,&nbsp;Julie Mollet ,&nbsp;David Guenoun ,&nbsp;Ariane Heydari-Olya ,&nbsp;Irvin Sautet ,&nbsp;Sihao Diao ,&nbsp;Valérie Faivre ,&nbsp;Julien Pansiot ,&nbsp;Lara Tabet ,&nbsp;Jennifer Hua ,&nbsp;Leslie Schwendimann ,&nbsp;Amazigh Mokhtari ,&nbsp;Rebeca Martin-Rosique ,&nbsp;Sead Chadi ,&nbsp;Mireille Laforge ,&nbsp;Charlie Demené ,&nbsp;Andrée Delahaye-Duriez ,&nbsp;Rochellys Diaz-Heijtz ,&nbsp;Bobbi Fleiss ,&nbsp;Cindy Bokobza","doi":"10.1016/j.bbi.2024.10.023","DOIUrl":"10.1016/j.bbi.2024.10.023","url":null,"abstract":"<div><div>Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 824-837"},"PeriodicalIF":8.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495346","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":"Prophylactic use of probiotics as an adjunctive treatment for ischemic stroke via the gut-spleen-brain axis","authors":"Yi-Hsin Wang ,&nbsp;Jiuan-Miaw Liao ,&nbsp;Ming-Shiou Jan ,&nbsp;Meilin Wang ,&nbsp;Hsing-Hui Su ,&nbsp;Wan-Hua Tsai ,&nbsp;Pei-Hsun Liu ,&nbsp;Yuang-Seng Tsuei ,&nbsp;Shiang-Suo Huang","doi":"10.1016/j.bbi.2024.10.026","DOIUrl":"10.1016/j.bbi.2024.10.026","url":null,"abstract":"<div><div>A growing body of research has focused on the role of spleen in orchestrating brain injury through the peripheral immune system following stroke, highlighting the brain-spleen axis as a potential target for mitigating neuronal damage during stroke. The gut microbiota plays a pivotal role in the bidirectional communication between the gut and the brain. Several studies have suggested that probiotic supplements hold promise as a strategic approach to maintaining a balanced intestinal microecology, reducing the apoptosis of intestinal epithelial cells, protecting the intestinal mucosal and blood–brain barrier (BBB), enhancing both intestinal and systemic immune functions, and thereby potentially affecting the pathogenesis and progression of ischemic stroke. In this study, we aimed to clarify the neuroprotective effects of supplementation with <em>Lactobacillus</em>, specifically <em>Limosilactobacillus</em> reuteri GMNL-89 (G89) and Lacticaseibacillus <em>paracasei</em> GMNL-133 (G133) on ischemic stroke and investigate how G89 and G133 modulate the communication mechanisms between the gut, brain, and spleen following ischemic stroke. We explored the neuroprotection and the underlying mechanisms of <em>Lactobacillus</em> supplementation in C57BL/6 mice subjected to permanent middle cerebral artery occlusion. Our results revealed that oral treatment with G89 or G133 alone, as well as oral administration combining G89 and G133<em>,</em> significantly decreased the infarct volume and improved the neurological function in mice with ischemic stroke. Moreover, G89 treatment alone preserved the tight junction integrity of gut barrier, while G133 alone and the combined treatment of G89 and G133 would significantly decreased the BBB permeability, and thereby significantly attenuated stroke-induced local and systemic inflammatory responses. Both G89 and G133 regulated cytotoxic T cells, and the balance between T helper 1 cells and T helper 2 cells in the spleen following ischemic stroke. Additionally, the combined administration of G89 and G133 improved the gut dysbiosis and significantly increased the concentration of short‐chain fatty acids. In conclusion, our findings suggest that G89 and G133 may be used as nutrient supplements, holding promise as a prospective approach to combat ischemic stroke by modulating the gut-spleen-brain axis.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 784-798"},"PeriodicalIF":8.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495349","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":"A systematic approach to identify gaps in neuroimmunology: TNF-α and fear learning deficits, a worked example","authors":"Elise J. Heesbeen ,&nbsp;Elisabeth Y. Bijlsma ,&nbsp;Tristan A. Risseeuw ,&nbsp;Ellen V.S. Hessel ,&nbsp;Lucianne Groenink","doi":"10.1016/j.bbi.2024.10.027","DOIUrl":"10.1016/j.bbi.2024.10.027","url":null,"abstract":"<div><h3>Background</h3><div>The pathophysiology of several neurodegenerative and neuropsychiatric disorders is linked to an altered immune system. However, it is often unclear how the immune system specifically affects these disorders since neuroimmune interactions are very complex. In this paper, we introduce an adjusted version of the adverse outcome pathway (AOP) approach from toxicology to the field of neuroimmunology. A review of the effect of TNF-α on fear learning deficits is used as a worked example to demonstrate how an AOP approach can help identify gaps of knowledge and crucial steps in the pathophysiology of neuroimmunological disorders.</div></div><div><h3>Methods</h3><div>The AOP was constructed in five steps. First, the adverse outcome was formulated clearly and specifically. Second, the link between the molecular initiating event and the adverse outcome was established with a preliminary literature search in the Medline database. Third, a systematic literature search was performed in which we identified 95 relevant articles. Fourth, the main biological processes and relevant key events were identified. Fifth, the links between key events were determined and an AOP network was constructed.</div></div><div><h3>Results</h3><div>We identified three pathways through which TNF-α may affect fear learning. First, TNF-α receptor activation increases NF-κB levels which increases oxidative stress levels and reduces the activity of glutamate transporters. This alters the synaptic plasticity which is associated with impaired fear acquisition, consolidation, and fear extinction. Second, activation of TNF-α receptors increases the expression and capacity of the serotonin transporter which is linked to impaired fear acquisition, expression, and extinction. Third, TNF-α receptor 1 activation can induce necroptosis, leading to neuroinflammation which is linked to fear learning deficits.</div></div><div><h3>Conclusion</h3><div>To successfully apply the AOP approach in neuroimmunology we recommend defining adverse outcomes more precisely, establishing stronger connections between key events from various biological processes, incorporating feedforward and feedback loops, and identifying more mechanistic knowledge in later key events. These adjustments are needed to map the complex processes within the field of neuroimmunology and to identify gaps of knowledge.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"123 ","pages":"Pages 752-764"},"PeriodicalIF":8.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495350","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":"Lifetime chronic stress Exposures, stress Hormones, and biological Aging: Results from the midlife in the United States (MIDUS) study.","authors":"Jenna L Hansen, Judith E Carroll, Teresa E Seeman, Steve W Cole, Kelly E Rentscher","doi":"10.1016/j.bbi.2024.10.022","DOIUrl":"10.1016/j.bbi.2024.10.022","url":null,"abstract":"<p><p>Psychosocial stress and adversity have been linked to accelerated aging and increased risk for age-related diseases. Animal and in vitro studies have shown that exposure to stress hormones (catecholamines, glucocorticoids) can impact biological aging processes such as DNA damage and cellular senescence, suggesting they play a key role in links between stress and aging; however, these associations have not been well investigated in humans. We examined cross-sectional associations between chronic stress exposures, stress hormones, and biological aging markers in midlife adults and whether stress hormones mediated associations between stress and aging. Participants were 531 adults aged 26-78 years (M_age = 53.9, 50.1 % female) in the nationally representative Midlife in the United States Refresher cohort. They reported chronic stress exposures in childhood and adulthood (Stressful Life Event Inventory) and provided 12-hour urine samples used to assess norepinephrine, epinephrine, and cortisol. RNA sequencing of peripheral blood mononuclear cells derived aging biomarkers: the DNA damage response (DDR; 30-gene composite), cellular senescence signal p16^INK4a (CDKN2A), and the pro-inflammatory senescence-associated secretory phenotype (SASP; 57-gene composite). Regression models adjusting for age, sex, race/ethnicity, BMI, smoking status, alcohol use, and medications revealed that more childhood exposures were associated with higher norepinephrine (β = 0.09, p = 0.04), independent from adult exposures. Higher norepinephrine was associated with elevated DDR expression (β = 0.17, p < 0.001). Higher norepinephrine (β = 0.14, p = 0.003) and epinephrine (β = 0.10, p = 0.02) were both associated with elevated SASP expression. Statistical mediation analyses implicated elevated norepinephrine as a plausible mediator of associations between childhood exposures and both DDR (unstandardized b = 0.005, 95 % CI [0.0002, 0.011]) and SASP (b = 0.002, 95 % CI [0.0001, 0.05]). Findings provide preliminary evidence in humans that stress hormones may impact key biological aging processes and may be a mechanism linking chronic stress exposures in childhood to accelerated aging later in life.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495347","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}