Brain, behavior, & immunity - health最新文献

{"title":"Social stress changes gut microbiome composition in male, female, and aggressor mice","authors":"Isabel Garcia ,&nbsp;Fatmanur Kilic ,&nbsp;Chris-Ann Bryan ,&nbsp;Jose Castro-Vildosola ,&nbsp;Sai Anusha Jonnalagadda ,&nbsp;Akhila Kasturi ,&nbsp;Jacqueline Tilly ,&nbsp;Jordyn Smith ,&nbsp;Sofia Valentin ,&nbsp;Sergio Moncayo ,&nbsp;Tamara Hala ,&nbsp;Eric Klein ,&nbsp;Brian F. Corbett","doi":"10.1016/j.bbih.2025.101138","DOIUrl":"10.1016/j.bbih.2025.101138","url":null,"abstract":"<div><div>Psychological stress causes gut dysbiosis, which is associated with adverse effects on physical and mental health in humans and mice. Identifying taxa of gut bacteria changed by stress, and whether stress differentially alters their relative abundance in males and females, has important implications for stress-related disorders. We modeled individual differences in resilience or susceptibility using the chronic social defeat stress (CSDS) paradigm. Here, C57BL/6 mice are exposed to a novel retired breeder CD-1 aggressor for 10 min per day for 10 days. In this paradigm, resilient and susceptible subpopulations can be identified using the social interaction paradigm following CSDS. Fecal samples were collected immediately following Day 1 and Day 10 of CSDS. 16S ribosomal RNA sequencing was used to identify the relative abundance of 200 bacteria species. We analyzed group differences in phyla, genera, and species in resilient, susceptible, and non-stressed control male and female C57/BL/6 intruders along with CD-1 aggressors. Stress reduced microbiome diversity and caused gut dysbiosis in all groups, including aggressors. These changes were not observed in non-stressed mice. CSDS altered the relative abundance of every gut bacteria phylum. CSDS reduced genera in the Firmicutes phylum whereas sex altered fewer genera. The relative abundance of an uncultured <em>Ruminococcus</em> species on Day 1 predicted social avoidance following CSDS, with a stronger correlation in stressed females compared to males. Together, our findings demonstrate that CSDS changes gut microbiome composition in male and female mice.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101138"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coordination of inflammatory and adrenocortical stress response during pregnancy and variation by mental health","authors":"Heidemarie K. Laurent ,&nbsp;Sherryl H. Goodman ,&nbsp;Douglas A. Granger ,&nbsp;Penina M. Backer","doi":"10.1016/j.bbih.2025.101145","DOIUrl":"10.1016/j.bbih.2025.101145","url":null,"abstract":"<div><div>Well-regulated coordination of a multi-system stress response is particularly consequential for intergenerational health during pregnancy, when maternal stress systems typically adapt to protect the fetus. However, little is known about patterns of combined immune/inflammatory mediator (IM) and hypothalamic-pituitary-adrenal (HPA) axis responding to acute stress in human pregnancy, let alone variations associated with maternal health risks. In this study we aimed to define normative perinatal stress response coordination and potential risk profiles by testing relations among pregnant women's salivary IM's and cortisol in response to psychosocial stress, as well as both concurrent affective distress symptomatology and lifetime diagnoses of affective disorders. A community sample of pregnant women (<em>n</em> = 158) participating in the first timepoint of a longitudinal study completed the Trier Social Stress Task and contributed five saliva samples assayed for cortisol; pro-inflammatory cytokines IL1β, IL6, TNFα; and CRP. They self-reported symptoms reflecting common (general distress) and distinct (anhedonic depression, anxious arousal) components of affective distress, and were interviewed about mental health history with a structured clinical interview. Multilevel modeling of IM and cortisol trajectories revealed IM and cortisol responses were positively coordinated on average, but varied across women. Greater affective distress predicted higher/increasing IM stress responses that diverged from cortisol recovery; history of mood disorder specifically related to increasing post-stress IM's, while current general distress related to non-coordination/divergence of IM from cortisol response. These findings highlight a novel stress response pathway characterizing both previous and current affective distress that may help efforts to ameliorate intergenerational impacts of perinatal stress.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101145"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early brain changes in Lyme disease are associated with clinical outcomes","authors":"Cherie L. Marvel ,&nbsp;Alison W. Rebman ,&nbsp;Kylie H. Alm ,&nbsp;Pegah Touradji ,&nbsp;Arnold Bakker ,&nbsp;Prianca A. Nadkarni ,&nbsp;Deeya Bhattacharya ,&nbsp;Owen P. Morgan ,&nbsp;Amy Mistri ,&nbsp;Christopher C. Sandino ,&nbsp;Jonathan A. Ecker ,&nbsp;Erica A. Kozero ,&nbsp;Arun Venkatesan ,&nbsp;Abhay Moghekar ,&nbsp;Ashar A. Keeys ,&nbsp;John N. Aucott","doi":"10.1016/j.bbih.2025.101153","DOIUrl":"10.1016/j.bbih.2025.101153","url":null,"abstract":"<div><div>In Lyme disease (LD), 10–20 % of patients develop persistent symptoms following antibiotic treatment (i.e., post-treatment Lyme disease (PTLD)), which often includes neurological symptoms. This study tested the hypothesis that physiological brain changes occur early in LD and influence outcomes.</div><div>Task-based functional MRI (fMRI) and health surveys were administered to patients with acute LD (n = 20) after treatment and six months later. Demographically matched healthy controls (HC; n = 19) were also assessed six months apart. The LD group was categorized at six months into those who had returned to health (RTH, n = 11) or reported persistent symptoms (sPTLD, n = 9). FMRI data from both LD subgroups were compared to each other and HC at both time points. FMRI-guided regions of interest (ROI) values were compared to health surveys.</div><div>Baseline brain activity in RTH was elevated in fronto-parietal regions relative to sPTLD (p &lt; .0025) and HC (p &lt; .001). Notably, 64 % of activation clusters in RTH were in white matter, confirmed by segmentation analysis. FMRI-guided ROI values from RTH vs. HC correlated with higher health survey scores. At 6-months, few group differences remained. By contrast, sPTLD vs. HC fMRI comparisons yielded few activation differences at either time point or correlations with health survey scores.</div><div>Robust brain activity in early LD was associated with future RTH. By contrast, the absence of early brain activity was associated with persistent symptoms, suggesting that failure to mount an early response contributes to PTLD. Understanding how brain activity relates to recovery in LD can aid prognosis and guide treatment.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101153"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal models of Huntington's disease. Pros and cons","authors":"Polina Stepanova ,&nbsp;Merja H. Voutilainen ,&nbsp;Ove Eriksson ,&nbsp;Dan Lindholm","doi":"10.1016/j.bbih.2025.101149","DOIUrl":"10.1016/j.bbih.2025.101149","url":null,"abstract":"<div><div>Modelling of human neurological diseases uses a plethora of ever-more sophisticated methods and approaches. For Huntington's disease (HD), which affects specific neuronal types and circuits in the brain, this has meant the use of both neurotoxic compounds and various animal models of different complexity, ranging from rodents to non-primate ones. Genetic models are classified based on the use of specific constructs including gene including gene fragments, full-length, knock-out and knock-in models. In this review, we will discuss the available animal models for HD, highlighting their pros and cons in studying the neuropathology, behavioural alterations, and biological mechanisms that prevail in HD and during the disease progression. We also highlight present knowledge gaps and difficulties to fully recapitulate the human disease. At the end we will further elaborate on current outstanding questions in HD research that warrant further studies using both animal models and patient data. This may help to guide future research and increase the translational relevance of the models to solve key questions and pave the way for better treatment options and design of drugs to alleviate the course of HD.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101149"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145684289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota–neuroinflammation axis: A new mechanism and therapeutic target for comorbid depression in epilepsy","authors":"Xiujuan wang ,&nbsp;Mu Liu ,&nbsp;Liuzhao Cao ,&nbsp;Hao Huang ,&nbsp;Juan Yang ,&nbsp;Haiqing Zhang ,&nbsp;chengyu pan ,&nbsp;Zucai Xu","doi":"10.1016/j.bbih.2025.101150","DOIUrl":"10.1016/j.bbih.2025.101150","url":null,"abstract":"<div><div>This review systematically summarizes the key pathological mechanisms and therapeutic potential of the gut microbiota–neuroinflammation axis in comorbid depression in epilepsy. Approximately 30–50 % of epilepsy patients suffer from depression, which leads to poor treatment adherence and significantly increases the risk of mortality and suicide. Studies have shown that dysbiosis of the gut microbiota and central nervous system inflammation interact through multiple pathways—including microbial metabolites, immune modulation, and the vagus nerve—to form a “gut–brain–emotion” regulatory network. Epilepsy patients often exhibit reduced diversity and abnormal composition of gut microbiota, most notably dysregulation of Firmicutes, which promotes systemic inflammation and activation of local central nervous system inflammation. Neuroinflammation, by affecting neurotransmitter metabolism, blood-brain barrier function, and neuroplasticity, exacerbates abnormal neuronal discharges and depressive symptoms, thereby creating a vicious cycle. Intervention strategies targeting this axis have shown promising prospects, including supplementation with probiotics or prebiotics, modulation of microbial metabolites, anti-inflammatory therapies, and dietary regulation, all of which can significantly improve both the frequency of epileptic seizures and emotional states. Multi-omics analysis and precise subtyping are advancing the development of individualized treatment plans, bridging the gaps among neuroscience, immunology, and microbiology. Although challenges remain in standardized sampling, causal mechanism validation, and long-term follow-up studies, the gut microbiota–neuroinflammation axis has emerged as a new frontier in the precise prevention and treatment of comorbid depression in epilepsy, providing a tangible theoretical foundation and practical strategies for improving patient outcomes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101150"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Internalized weight stigma, metabolic syndrome, and inflammation in postmenopausal women with obesity","authors":"Rebecca L. Pearl ,&nbsp;Stephen D. Anton ,&nbsp;Danielle Saunders ,&nbsp;Marian Hernandez ,&nbsp;Laurie C. Groshon ,&nbsp;Miriam Sheynblyum ,&nbsp;Dakota L. Leget ,&nbsp;Christian McLaren ,&nbsp;Sarah Vial ,&nbsp;Lecsy Gonzalez ,&nbsp;Kevin Wu ,&nbsp;Gayane Barsamyan ,&nbsp;Thomas A. Wadden","doi":"10.1016/j.bbih.2025.101129","DOIUrl":"10.1016/j.bbih.2025.101129","url":null,"abstract":"<div><h3>Objective</h3><div>To determine the relationship of internalized weight stigma with metabolic syndrome (MetS) and markers of inflammation.</div></div><div><h3>Methods</h3><div>Postmenopausal women with obesity (<em>N</em> = 101) with high or low scores on the Weight Bias Internalization Scale completed a single assessment visit. MetS components (waist circumference, blood pressure, triglycerides, HDL cholesterol, and glucose) were measured, along with body mass index (BMI). Blood samples were drawn to analyze C-reactive protein, interleukin-6, and myeloperoxidase. Participants completed a second measure of internalized weight stigma (Weight Self-Stigma Questionnaire; WSSQ) and reported medications, demographics, depression symptoms, smoking status, and perceived stress (included as covariates).</div></div><div><h3>Results</h3><div>Logistic regression showed no significant relationship between either measure of internalized weight stigma and MetS when controlling for BMI, depression, and demographics. A small, significant, positive association emerged between WSSQ scores and MetS when adding the covariate of anti-depressant medication (OR = 1.07, <em>p</em> = 0.040). WSSQ scores were associated with significantly greater odds of having high blood pressure (OR = 1.10, <em>p</em> = 0.003) and low HDL cholesterol (OR = 1.06, <em>p</em> = 0.030). Both measures of internalized weight stigma were associated with greater continuous blood pressure values. Inflammatory markers were not associated with internalized weight stigma in most analyses.</div></div><div><h3>Conclusions</h3><div>Some significant associations were found between internalized weight stigma and MetS components, but more research is needed to clarify these relationships.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101129"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotonin and neurofilament light chain in alcohol-related suicide: Preliminary case observations","authors":"Shao-Cheng Wang ,&nbsp;Chih-Hui Wang ,&nbsp;Tung-Hsia Liu ,&nbsp;Hsian-Wei Kuo ,&nbsp;Yu-Li Liu","doi":"10.1016/j.bbih.2025.101136","DOIUrl":"10.1016/j.bbih.2025.101136","url":null,"abstract":"<div><div>Alcohol dependence significantly impacts both physiological and psychological health and is strongly linked to increased suicide attempt. However, the neurobiological mechanisms connecting alcohol use disorder (AUD) to suicidality remain inadequately understood. This study evaluated the severity of alcohol dependence in 24 patients diagnosed with AUD using the Alcohol Use Disorders Identification Test (AUDIT). In parallel, peripheral blood levels of neurofilament light chain (NfL), a bioindicator of neuronal injury, and serotonin, a neurotransmitter implicated in mood regulation and suicidality, were quantified. One patient with a prior history of suicide attempts exhibited markedly elevated plasma NfL levels (1350 pg/ml), greatly exceeding the mean observed in non-suicidal AUD patients (33.06 pg/ml). Despite the absence of detectable brain abnormalities on imaging, the patient presented with a lumbar vertebral burst fracture, suggesting spinal cord trauma as the source of neuronal injury. Moreover, serotonin levels in this individual were substantially reduced (89.41 ng/ml) relative to the group average (340.5 ng/ml). These findings suggest that elevated NfL levels may reflect neural injury originating from spinal, rather than cerebral, sources in AUD patients with suicide attempts. Additionally, reduced serotonin levels may serve as a clinically useful bioindicator to stratify suicide attempt in this population.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101136"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between body mass index, gray matter volume and peripheral inflammation in patients with post-COVID condition","authors":"Luise Victoria Claaß ,&nbsp;Franziska Schick ,&nbsp;Tonia Rocktäschel ,&nbsp;Alejandra P. Garza ,&nbsp;Christian Gaser ,&nbsp;Philipp A. Reuken ,&nbsp;Andreas Stallmach ,&nbsp;Kathrin Finke ,&nbsp;Sharmili Edwin Thanarajah ,&nbsp;Martin Walter ,&nbsp;Ildiko Rita Dunay ,&nbsp;Bianca Besteher ,&nbsp;Nils Opel","doi":"10.1016/j.bbih.2025.101137","DOIUrl":"10.1016/j.bbih.2025.101137","url":null,"abstract":"<div><h3>Background</h3><div>Obesity, a condition associated with low-grade peripheral inflammation, is an independent risk factor for severe COVID-19 and has been linked to structural brain alterations. Given that post-COVID condition (PCC) is also associated with structural brain abnormalities and lingering immunological alterations, this study aimed to assess whether obesity contributes to these neural and immunological differences in PCC patients.</div></div><div><h3>Methods</h3><div>We investigated a previously established cohort of PCC patients (n = 61), recruited between April 2021 and June 2022. Whole-brain comparison of gray matter volume (GMV) was conducted by voxel-based morphometry (VBM). Obesity, as measured by body mass index (BMI), as well as age, sex, and total intracranial volume (TIV), were included as regressors in a linear model. Signature immunological markers were quantified in 50 participants using a LEGENDplex™ multiplex bead-based assay.</div></div><div><h3>Results</h3><div>A significant negative association was found between BMI and GMV in the right thalamus (p(FWE) = 0.039, k = 209, TFCE = 1037.97, x = 18, y = −21, z = 8). Moreover, BMI and thalamic GMV were significantly associated with immunological markers in PCC. Specifically, BMI was positively associated with Interleukin-6 (p = 0.021) and negatively with Interleukin-7 (p = 0.021), while GMV showed positive associations with Interleukin-8 (p = 0.05).</div></div><div><h3>Conclusion</h3><div>The results suggest that BMI contributes to GMV alterations in PCC patients, with both BMI and GMV demonstrating correlations with peripheral immunological markers. These findings indicate that converging mechanisms involving inflammation and structural brain alterations may contribute to obesity and PCC.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101137"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moderating effects of individual factors on the relationship between inflammation and psychophysiological states in healthy adults","authors":"Kao Yamaoka ,&nbsp;Yuri Ishii ,&nbsp;Yuri Terasawa","doi":"10.1016/j.bbih.2025.101135","DOIUrl":"10.1016/j.bbih.2025.101135","url":null,"abstract":"<div><div>Systemic inflammation affects psychological processes. Although the association between inflammation and psychophysiological state has been extensively investigated in patients with depression or inflammatory disease, how this relationship manifests in healthy individuals is not clearly known. Not all individuals exhibit distress in response to elevated inflammatory markers, suggesting the presence of psychological moderators. Elucidating the effect of elevated inflammatory markers on healthy adults would broaden the understanding of the relationship between inflammation and psychophysiological state. We investigated the moderating effect of individual factors, including emotion regulation, sleep quality, and interoceptive awareness, on the relationship between inflammatory markers and psychophysiological states in healthy adults. A total of 155 participants aged 30–59 years were assessed for inflammatory markers, individual factors, and subjective psychological and physical symptoms. Hierarchical regression and interaction models revealed that individuals with poor emotion regulation or low-quality sleep showed stronger associations between inflammatory markers and symptoms such as fatigue, somatic complaints, depression, and anxiety. Conversely, individuals with effective emotion regulation or high-quality sleep exhibited attenuated or even reversed associations, suggesting protective effects. Interoceptive awareness showed weaker and more context-dependent moderating effects. These results highlight the importance of psychological traits in modulating the effects of inflammation on mental and physical well-being in clinically healthy adults. Targeted interventions for enhancing emotion regulation and sleep quality may mitigate the psycho-physiological burden of inflammation and reduce the risk of future disease onset. The findings underscore the need for individualized psychoneuroimmunological models that incorporate trait-level moderators to explain variability in stress-related health outcomes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101135"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E.coli-derived CsgA-peptides stimulate cytokine production in microglia and lead to transient changes in neocortical Aβ-levels in pre-plaque APPSWE/PS1ΔE9 and wild type mice","authors":"Leda Mygind ,&nbsp;Gabriel Jensen ,&nbsp;Victoria Neesgaard ,&nbsp;Katrine Tækker Krohn ,&nbsp;Serges Torres Puig ,&nbsp;Anders Boysen ,&nbsp;Sussanne Petersen ,&nbsp;Kate Lykke Lambertsen ,&nbsp;Athanasios Metaxas ,&nbsp;Michael Kemp ,&nbsp;Jakob Møller-Jensen ,&nbsp;Bente Finsen","doi":"10.1016/j.bbih.2025.101128","DOIUrl":"10.1016/j.bbih.2025.101128","url":null,"abstract":"<div><div>Epidemiological and pre-clinical data propose that infections can accelerate the cognitive decline in Alzheimer's disease (AD) and other dementias. The implication of infectious agents, and especially the role of <em>E.coli</em> and other amyloid-peptide producing bacteria, on the development and progression of cerebral amyloidosis and neuroinflammation, both key neuropathological characteristics of AD, has only been studied to a limited extent.</div><div>In this study, recombinant bacterial amyloid surface protein CsgA was injected intracisternally in pre-plaque 8-11-week-old <em>APP</em>_<em>SWE</em><em>/PS1</em>_{<em>ΔE9</em>} mice and age-matched <em>wild type</em> (<em>WT</em>) mice. Although less potent than bacterial lipopolysaccharide, CsgA significantly increased the gene expression of inflammatory cytokines, such as tumor necrosis factor, in the neocortex of both <em>APP</em>_<em>SWE</em><em>/PS1</em>_{<em>ΔE9</em>} and <em>WT</em> mice, and in cultured microglia. CsgA exposure also induced transient changes in neocortical amyloid-beta (Aβ) peptide levels, increasing the highly fibrillogenic Aβ₄₂ in the guanidine-fraction in <em>APP</em>_<em>SWE</em><em>/PS1</em>_{<em>ΔE9</em>} mice and decreasing Aβ₄₀ in the PBS-fraction in <em>WT</em> mice. The changes in Aβ levels had dissipated 24 h post-injection. In line with the only transient changes in Aβ levels and inflammatory gene expression, CsgA did not impact on long term spatial memory in pre-plaque <em>APP</em>_<em>SWE</em><em>/PS1</em>_{<em>ΔE9</em>} mice.</div><div>Our findings highlight a contribution of bacterial amyloid proteins on neuroinflammation and a possible contribution in influencing Aβ-homeostasis during infections. However, findings need to be further elaborated in older <em>APP</em>_<em>SWE</em><em>/PS1</em>_{<em>ΔE9</em>} mice in which Aβ plaques are abundant and an inflammatory response already established. Also, the impact of CsgA and other bacterial amyloids should be examined after repeated and/or continuous administration and at different concentrations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101128"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145428835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}