Brain, behavior, & immunity - health最新文献

{"title":"Prophylactic clemastine treatment improves influenza A virus-induced cognitive dysfunction in mice.","authors":"J.D. Tingling ,&nbsp;S.A. Krauklis ,&nbsp;P.L. Haak ,&nbsp;R. Carr ,&nbsp;A.Y. Louie ,&nbsp;R.W. Johnson ,&nbsp;A.J. Steelman","doi":"10.1016/j.bbih.2024.100891","DOIUrl":"10.1016/j.bbih.2024.100891","url":null,"abstract":"<div><div>Respiratory infection by influenza A virus (IAV) is known to cause systemic inflammation, neuroinflammation, and cognitive impairment. We previously found that experimental infection with IAV affected oligodendrocyte homeostasis, which was associated with altered expression of genes involved in myelin maintenance as well as the lipidome. In this study, we sought to determine if clemastine, an antihistamine with myelin promoting properties, could reverse the effects of IAV on oligodendrocyte (OL) specific genes, as well as mitigate infection-induced cognitive impairment. Male and female C57BL/6J mice were randomized into experimental groups based on clemastine treatment, infection, and sex. Treatment with vehicle or clemastine (10mg/kg/d) commenced seven days prior to inoculation with either saline or IAV and continued throughout the experiment. Body weight was measured throughout the infection. Spatial learning and memory were assessed by Morris water maze. Sickness behavior was assessed by measuring burrowing response. Immune cell responses were determined by flow cytometry, RT-qPCR, antigen recall assays and ELISA, and viral load assessed by RT-qPCR. Hippocampal levels of neuroinflammatory (<em>Tnf, Cdkn1a</em>) and myelin (<em>Plp1</em>, <em>Mag</em>, <em>Ugt8a</em>) genes were determined by RT-qPCR. Mice infected with IAV developed weight loss, impaired cognitive flexibility, reduced burrowing behavior, altered lung immune cell infiltration, increased circulating anti-viral IgM and IgG levels and increased T cell responses to IAV epitopes. Infection increased hippocampal levels of genes associated with neuroinflammation and decreased levels of genes involved in myelination. Clemastine treatment resulted in earlier recovery of weight loss in males and increased IgM levels for both sexes, but neither affected expression levels of <em>Tnf</em> or <em>Cdkn1a</em>, nor rescued changes to oligodendrocyte genes. However, treatment mitigated infection-induced neurocognitive impairment.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100891"},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of light on Interleukin-10: A preliminary study","authors":"Liza Mekschrat ,&nbsp;Michael Göring ,&nbsp;Bjarne Schmalbach ,&nbsp;Nicolas Rohleder ,&nbsp;Katja Petrowski","doi":"10.1016/j.bbih.2024.100887","DOIUrl":"10.1016/j.bbih.2024.100887","url":null,"abstract":"<div><div>Light influences circadian rhythms, including that of the stress hormone cortisol. Cortisol, in turn, has been observed to promote expression of the anti-inflammatory cytokine IL-10. It is thus of interest whether the cytokine IL-10 is also influenced by light, perhaps in accord with the diurnal variations in cortisol. Hence, this highly standardized preliminary sleep laboratory study in healthy adult men investigated a potential influence of different light exposure on IL-10 and cortisol concentrations in blood. In a between-subject design, <em>N</em> = 42 participants were exposed to either bright, dim, blue or red light after wake-up. Two mixed-model analyses with the factors of light condition and time (across eight IL-10 and cortisol sampling points) were conducted. Additionally, area under the curve measurements (AUCg and AUCi) were calculated for both cortisol and IL-10. Across all conditions, IL-10 and cortisol concentrations significantly changed over time. However, none of the light conditions exerted a greater influence on IL-10 or cortisol levels than others. For cortisol, there was greater total output (AUCg) in the blue-light condition in particular. Further research is needed to gain insight into whether or not types of light or cortisol levels have a hand in influencing natural IL-10 concentrations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100887"},"PeriodicalIF":3.7,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heart rate variability and perinatal depressive symptoms: A scoping review protocol","authors":"Claudio Singh Solorzano ,&nbsp;Marta Spinoni ,&nbsp;Maria Grazia Di Benedetto ,&nbsp;Alessandra Biaggi ,&nbsp;Moira Marizzoni ,&nbsp;Elena Gatti ,&nbsp;Cristina Festari ,&nbsp;Michela Pievani ,&nbsp;Caterina Grano ,&nbsp;Annamaria Cattaneo","doi":"10.1016/j.bbih.2024.100885","DOIUrl":"10.1016/j.bbih.2024.100885","url":null,"abstract":"<div><h3>Objective</h3><div>An emerging marker of depression in the perinatal period is represented by a reduction in the autonomic nervous system (ANS) activity, reflected by heart rate variability (HRV). This scoping review aims to map the association between HRV and depression during the perinatal period and to understand its potential clinical implications.</div></div><div><h3>Introduction</h3><div>Previous evidence associated ANS dysfunction and depressive symptomatology in the general population. Few observational and intervention studies investigated how HRV could be related to both pre- and post-partum depressive symptoms. However, high heterogeneity in the study designs and methods has been reported. Therefore, this scoping review plans to combine all these findings to build a starting point for future research.</div></div><div><h3>Inclusion criteria</h3><div>This scoping review will consider articles focusing on the association between HRV and depression in the peripartum and – when available – on the impact of interventions on HRV and how this correlates with changes in depressive symptoms. Studies will be included with no restrictions on participants’ age, peripartum time points for the assessment, and HRV parameters collected.</div></div><div><h3>Methods</h3><div>We will perform a systematic search using the Medline (PubMed), PsychInfo, and Web of Science (WoS) databases. Two authors will independently screen titles, abstracts, and then full-text articles that meet the inclusion criteria. The review will include only journal articles published in English, with no time limitations. Data will be extracted and presented in tables and/or graphical representations to summarise and describe the results. Extracted data will be reported in a comprehensive summary.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100885"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mind, brain, and body study: A protocol for examining the effects of the gut-brain-immune axis on internalizing symptoms in youth exposed to caregiving-related early adversity","authors":"Shiba M. Esfand ,&nbsp;Francesca R. Querdasi ,&nbsp;Naomi N. Gancz ,&nbsp;Paul W. Savoca ,&nbsp;Siyan Nussbaum ,&nbsp;Jennifer A. Somers ,&nbsp;Julia Ditzer ,&nbsp;Matthew B. Figueroa ,&nbsp;Kristen Chu ,&nbsp;Emily Towner ,&nbsp;Bridget L. Callaghan","doi":"10.1016/j.bbih.2024.100880","DOIUrl":"10.1016/j.bbih.2024.100880","url":null,"abstract":"<div><div>Experiences of caregiving-related adversity are common and one of the strongest predictors of internalizing psychopathology (i.e., anxiety and depression). Specifically, individuals who have been exposed to such early adversities have altered affective neurodevelopment, impaired memory systems, increased risk of developing internalizing disorders, greater inflammation, and differences in gastrointestinal (gut) microbiome composition. Crucially, the gut microbiome undergoes a sensitive period of development that precedes neural and immune sensitive periods, thus making it a potentially fruitful target for intervention. Though previous work has assessed neural, immune, and gut microbiome systems in individuals exposed to early adversity, studies have primarily looked at these biological systems independently. The Mind, Brain, and Body study (MBB) implements multimodal and longitudinal design to assess how changes in the gut microbiome following caregiving-related adversity may underlie altered affective neurodevelopment, memory, and immune functioning in youth and contribute to internalizing symptoms. Across three waves, spread approximately 12–18 months apart, youth with and without previous experiences of caregiving-related adversity completed self-report measures of mental and physical health, provided stool, saliva, hair, and blood samples, and completed an MRI scan. Results of this study will expand our knowledge on how the gut microbiome shapes several biological and cognitive systems and motivate future work investigating the gut microbiome as potential target for intervention.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100880"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of interleukin-6 in the association between inflammation and cognitive performance in obstructive sleep apnea","authors":"Mariana Fernandes ,&nbsp;Matteo Spanetta ,&nbsp;Giorgio Vetrugno ,&nbsp;Marzia Nuccetelli ,&nbsp;Fabio Placidi ,&nbsp;Alessandro Castelli ,&nbsp;Natalia Manfredi ,&nbsp;Francesca Izzi ,&nbsp;Giuseppina Laganà ,&nbsp;Sergio Bernardini ,&nbsp;Nicola Biagio Mercuri ,&nbsp;Claudio Liguori","doi":"10.1016/j.bbih.2024.100875","DOIUrl":"10.1016/j.bbih.2024.100875","url":null,"abstract":"<div><h3>Background</h3><div>Interleukin-6 (IL-6) represents one of the main molecules involved in inflammatory responses, which can be altered in either patients with cognitive impairment or obstructive sleep apnea (OSA). The present study aimed to evaluate serum IL-6 levels and cognitive performance in patients with severe OSA (Apnea-Hypopnea Index - AHI &gt;30/h).</div></div><div><h3>Methods</h3><div>Thirty patients with severe OSA were compared to 15 controls similar in age, sex, and Body Mass Index. All patients underwent a sleep medicine interview, including the Epworth Sleepiness Scale (ESS), a polygraphic cardiorespiratory recording, the Montreal Cognitive Assessment (MoCA), and a blood sample for serum IL-6 assessment.</div></div><div><h3>Results</h3><div>OSA patients presented higher IL-6 serum levels (Md = 7.38) than controls (Md = 2.20, p &lt; 0.001). Moreover, OSA patients showed lower MoCA (Md = 27.00) and higher ESS scores (Md = 8.00) than controls (Md = 30.00, p &lt; 0.001; Md = 4.00, p = 0.004, respectively). Higher IL-6 serum levels were associated with lower oxygen saturation parameters and MoCA scores.</div></div><div><h3>Conclusions</h3><div>This study documented an association between inflammation, featured by higher IL-6 serum levels, and both nocturnal hypoxemia and cognitive impairment in OSA patients. Therefore, the increase in IL-6 levels may represent the result of vascular damage and neuroinflammation due to intermittent nocturnal hypoxia and further causing neurocognitive dysfunction in OSA.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100875"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying methamphetamine use predictors in HIV infection: Immune-dopaminergic signatures in peripheral leukocytes and the role of COMT genotype","authors":"Liana V. Basova ,&nbsp;Tera Riley ,&nbsp;Donald Franklin ,&nbsp;Violaine Delorme-Walker ,&nbsp;Wei Ling Lim ,&nbsp;Igor Grant ,&nbsp;Scott L. Letendre ,&nbsp;Jennifer E. Iudicello ,&nbsp;Mariana Cherner ,&nbsp;Ronald J. Ellis ,&nbsp;Maria Cecilia Garibaldi Marcondes","doi":"10.1016/j.bbih.2024.100873","DOIUrl":"10.1016/j.bbih.2024.100873","url":null,"abstract":"<div><div>The pursuit of translational biomarkers is complex due to the heterogeneous human pathophysiology, but critical for disease diagnosis, prognosis, monitoring therapeutic efficacy, and for patient stratification. In HIV-associated neurocognitive impairment (NCI), biomarkers that delineate the trajectory of neuropathogenesis and neurocognitive sequelae are critical, particularly considering confounders such as substance use, including Methamphetamine (METH). METH use is a significant health concern among persons living with HIV (PWH), aggravating cognitive deficits and neuroinflammation despite of antiretrovirals, introducing elements in the microenvironment that are fundamentally differerent in relation to non-METH users, such as high levels of dopamine (DA) affecting HIV-innate immune targets. Yet, current biomarkers do not detect these differences. We hypothesized that predefined DA-induced signatures detectable in peripheral blood leukocytes, can distinguish HIV+ METH users compared to HIV-negative or PWH that are non METH users. The elevated expression of CD8A, CREBBP, CCL5, and combinations of dopaminergic pathway transcripts clustered METH users with detectable CSF viral load and major depressive disorder (MDD), indicating neuroimmune-mechanistic links. Cathecol-o-methyltransferase (COMT) gene polymorphisms affecting DA metabolism improved the identification of PWH using METH with biomarkers. The results indicate that underlying immunedopaminergic mechanisms provide signatures and genotypes that can identify PWH that are METH users and their attributes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100873"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and depression: A study protocol to dissect pathogenetic mechanisms in the onset, comorbidity and treatment response","authors":"Catia Scassellati ,&nbsp;Nadia Cattane ,&nbsp;Francesco Benedetti ,&nbsp;Tiziana Borsello ,&nbsp;Giuseppe Cicala ,&nbsp;Massimo Gennarelli ,&nbsp;Patrizia Genini ,&nbsp;Alessandro Gialluisi ,&nbsp;Arianna Giani ,&nbsp;Licia Iacoviello ,&nbsp;Alessandra Minelli ,&nbsp;Edoardo Spina ,&nbsp;Benedetta Vai ,&nbsp;Erika Vitali ,&nbsp;Annamaria Cattaneo","doi":"10.1016/j.bbih.2024.100886","DOIUrl":"10.1016/j.bbih.2024.100886","url":null,"abstract":"<div><div>About one third of patients suffering from Major Depressive Disorder (MDD) do not respond to any antidepressant medications and 75% experience relapses and general health deterioration. Importantly, inflammation can contribute to such negative outcomes, as well as to cause depression in patients who have been exposed to adverse childhood experiences and/or to viral infections, including COVID-19. Depressed patients also have an increased risk for developing comorbidities, such as cardio-metabolic dysfunctions, where inflammatory alterations, again, play a role in connecting MDD and these comorbid conditions.</div><div>Here, we present our study protocol funded by the Italian Ministry of Health in the context of the PNRR call (M6/C2_CALL 2022; Project code: PNRR-MAD-2022-12375859). The project aims to clarify the role of inflammation: i) in the onset of depression in association with environmental factors; ii) in the mechanisms associated with treatment response/resistance; iii) in depression and its comorbidity. To reach all these aims, we will perform biochemical, transcriptomic, genetic variants analyses on inflammatory/immune genes, pharmacokinetics and machine learning techniques, taking advantage of different human cohorts (adolescent depressed patients exposed to childhood trauma; adult depressed patients; treatment resistant depression patients; both prevalent and incident depression cases identified within a large population cohort). Moreover, we will use <em>in vitro</em> models (primary cultures of astrocytes, neurons and microglia) treated with pro-inflammatory or stressful challenges and preventive compounds to clarify the underlying mechanisms.</div><div>This 2-years project will increase the knowledge on the role of inflammation in the prevention and treatment of MDD and in comorbid disorders, and it will also provide experimental evidence for the development of novel targets and tools for innovative personalized intervention strategies.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100886"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and cognitive performance in elite athletes: A cross-sectional study","authors":"Kati Wiedenbrüg ,&nbsp;Laura Will ,&nbsp;Lukas Reichert ,&nbsp;Sebastian Hacker ,&nbsp;Claudia Lenz ,&nbsp;Karen Zentgraf ,&nbsp;Markus Raab ,&nbsp;Karsten Krüger","doi":"10.1016/j.bbih.2024.100872","DOIUrl":"10.1016/j.bbih.2024.100872","url":null,"abstract":"<div><div>Functional cognition is relevant for athletic success and interdependent with physical exercise, yet despite repeatedly demonstrated inflammatory responses to physical training, there are no studies addressing the relationship between cognition and inflammation in athletes. The aim of this study was to investigate the relationship between cognitive performance and selected inflammatory, and further physiological biomarkers in elite athletes. Data from 350 elite athletes regarding cognitive performance (processing speed, selective attention, working memory, cognitive flexibility), systemic inflammatory markers, metabolic hormones, growth factors, tissue damage markers, and micronutrients (e.g., ferritin, 25-OH-vitamin D), as well as physiological, subjective ratings of recovery and stress were analysed by correlative and multiple regression analyses. Results show that across all athletes variance in processing speed, selective attention, and working memory, could be best explained through a combination of metabolic hormones with physiological and psychological indicators of stress, and in cognitive flexibility through vitamin D levels. Only for the subgroup of athletes from closed-skill sports, the ratio TNF-α:IL-10 significantly contributed to explanation of variance in working memory and cognitive flexibility. In general, found correlations point to the importance of inflammatory balance and sufficient long-term nutrient supply for unaffected cognitive performance.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100872"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Extension to the stress-buffering model: Timing of support across the lifecourse","authors":"Phoebe H. Lam","doi":"10.1016/j.bbih.2024.100876","DOIUrl":"10.1016/j.bbih.2024.100876","url":null,"abstract":"<div><div>Children and adolescents exposed to severe stressors exhibit poorer health across the lifespan. However, decades of research evaluating the Stress-Buffering model suggests that social support can attenuate stressors' negative impacts. Psychoneuroimmunology research in this area has shifted from asking whether support buffers stress to when and why support would succeed (or fail) to confer protection. This article takes a lifecourse perspective and proposes that timing of support may shape support's protective value by defining the type of protection that is provided and its operating mechanisms. Specifically, it considers three temporal scenarios: support that occurs during, after, or before stressor exposure. When support intervenes at the same developmental stage as the stressor (concurrent support), buffering effects occur wherein support prevents the development of intermediary mechanisms that reflect or increase disease risk; when support is present at a developmental stage before stressor exposure (prior support), banking effects occur such that support intervenes indirectly by fortifying the individual with resilience-promoting characteristics that in turn prevents the development of intermediary mechanisms; finally, when support arrives at a developmental stage after stressor exposure (later support), counteracting effects occur such that support offsets the impacts of intermediary mechanisms on diseases. It further posits that a match between timing of support and the linkage of interest (e.g., the stressor-mechanism path vs. the mechanism-disease path) is necessary for successful protection. The present paper discusses these postulations, reviews nascent evidence, and proposes future directions.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100876"},"PeriodicalIF":3.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life obesogenic environment integrates immunometabolic and epigenetic signatures governing neuroinflammation","authors":"Perla Ontiveros-Ángel ,&nbsp;Julio David Vega-Torres ,&nbsp;Timothy B. Simon ,&nbsp;Vivianna Williams ,&nbsp;Yaritza Inostroza-Nives ,&nbsp;Nashareth Alvarado-Crespo ,&nbsp;Yarimar Vega Gonzalez ,&nbsp;Marjory Pompolius ,&nbsp;William Katzka ,&nbsp;John Lou ,&nbsp;Fransua Sharafeddin ,&nbsp;Ike De la Peña ,&nbsp;Tien Dong ,&nbsp;Arpana Gupta ,&nbsp;Chi T. Viet ,&nbsp;Marcelo Febo ,&nbsp;Andre Obenaus ,&nbsp;Aarti Nair ,&nbsp;Johnny D. Figueroa","doi":"10.1016/j.bbih.2024.100879","DOIUrl":"10.1016/j.bbih.2024.100879","url":null,"abstract":"<div><div>Childhood overweight/obesity is associated with stress-related psychopathology, yet the pathways connecting childhood obesity to stress susceptibility are poorly understood. We employed a systems biology approach with 62 adolescent Lewis rats fed a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a control diet (CD, 13% kcal from fat). A subset of rats underwent a 31-day model of predator exposures and social instability (PSS). Effects were assessed using behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), 16S rRNA gene sequencing for gut microbiome profiling, hippocampal microglia analysis, and targeted gene methylation. Parallel experiments on human microglia cells (HMC3) examined how palmitic acid influences cortisol-related inflammatory responses.</div><div>Rats exposed to WD and PSS exhibited deficits in sociability, increased fear/anxiety-like behaviors, food consumption, and body weight. WD/PSS altered hippocampal microstructure (subiculum, CA1, dentate gyrus), and microbiome analysis showed a reduced abundance of members of the phylum <em>Firmicutes</em>. WD/PSS synergistically promoted neuroinflammatory changes in hippocampal microglia, linked with microbiome shifts and altered <em>Fkbp5</em> expression/methylation. In HMC3, palmitate disrupted cortisol responses, affecting morphology, phagocytic markers, and cytokine release, partially mediated by FKBP5.</div><div>This study identifies gene-environment interactions that influence microglia biology and may contribute to the connection between childhood obesity and stress-related psychopathology later in life.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100879"},"PeriodicalIF":3.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}