Brain, Behavior, and Immunity最新文献

{"title":"A Novel Aβ B-cell epitope Vaccine, Aβ1-10 with carrier protein OVA and KLH reduce Aβ-induced neuroinflammation mediated neuropathology in mouse model of Alzheimer’s disease","authors":"Jun Sung Park ,&nbsp;Kyonghwan Choe ,&nbsp;Riaz Ahmad ,&nbsp;Hyun Young Park ,&nbsp;Min Hwa Kang ,&nbsp;Tae Ju Park ,&nbsp;Myeong Ok Kim","doi":"10.1016/j.bbi.2025.06.001","DOIUrl":"10.1016/j.bbi.2025.06.001","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque deposition and neurofibrillary tangles, which collectively drive neuroinflammation, synaptic dysfunction, and cognitive decline. Here, we investigated whether a peptide epitope vaccine targeting the Aβ1–10 sequence could mitigate Aβ-induced pathology in AD mouse model. Three Aβ1–10 peptides, i.e. Aβ1–10-N, Aβ1–10-D1H, and Aβ1–10-S8R were synthesized, and Aβ1–10-S8R was further conjugated to ovalbumin (OVA) or keyhole limpet hemocyanin (KLH) to enhance immunogenicity. Among seven treatment groups, Aβ1–10-D1H and Aβ1–10-S8R, particularly when conjugated to OVA or KLH, effectively suppressed Aβ, amyloid-beta precursor protein (APP), and beta-secretase 1 (BACE-1) expression, decreased inflammatory cytokine production by astrocytes and microglia, and increased the levels of key synaptic markers (synaptophysin, synaptosomal-associated protein 23 [SNAP-23], postsynaptic density protein 95 [PSD-95]). Carrier protein conjugation also elevated immunoglobulin G (IgG) levels in the spleen, indicative of a robust humoral response. Taken together, these findings demonstrate that Aβ1–10-based immunization, especially with OVA or KLH conjugation, reduces Aβ-driven neuroinflammation, synaptic dysfunction, and memory deficits, suggesting a promising immunotherapeutic strategy for AD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 196-205"},"PeriodicalIF":8.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246519","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":"Prenatal poly(I:C) exposure, rather than altered maternal care, causes offspring behavioural and cognitive deficits in a rat model of neurodevelopmental disorders","authors":"Harry G. Potter ,&nbsp;Rebecca M. Woods ,&nbsp;Jarred M. Lorusso ,&nbsp;Grace Revill ,&nbsp;Michael K. Harte ,&nbsp;Jocelyn D. Glazier ,&nbsp;Joanna C. Neill ,&nbsp;Reinmar Hager","doi":"10.1016/j.bbi.2025.06.005","DOIUrl":"10.1016/j.bbi.2025.06.005","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive deficits are core features of neurodevelopmental disorders (NDD), arising from interacting genetic and environmental (GxE) factors. Maternal immune activation (MIA) is an established environmental risk factor, differentially affecting offspring cognition depending on exposure timing and severity. Maternal pro-inflammatory cytokines (e.g. tumor necrosis factor-alpha, TNFα) and altered maternal-offspring interactions are both implicated in MIA-induced NDD pathogenesis, but their relative impact on offspring cognition remains unclear. Understanding these mechanisms is crucial for developing targeted therapies for NDD-related cognitive deficits.</div></div><div><h3>Methods</h3><div>We used a split-litter cross-fostering design in a validated rat MIA model to examine prenatal and postnatal maternal influences on NDD-related cognitive traits. MIA was induced in pregnant Wistar dams (N = 22; gestational day 15) followed by cross-fostering (postnatal day (PD)1). Maternal behaviours, offspring ultrasonic vocalisations (USV), and cognition were assessed in both sexes. Phenotypic clustering of USV and cognitive traits was performed, and high-throughput Western blot quantified glutamic acid decarboxylase-67 (GAD67) and parvalbumin (PVALB) expression in the adult prefrontal cortex (PFC).</div></div><div><h3>Results</h3><div>Prenatal MIA, but not postnatal rearing, increased offspring USVs, maternal care behaviours, and impaired adult cognitive flexibility without affecting sociability. Offspring clustered into three groups based on PD10 USVs, with high USVs associated with reduced PD100 sociability. MIA did not alter PFC GAD67/PVALB expression.</div></div><div><h3>Conclusions</h3><div>The prenatal maternal response to MIA drives developmental and cognitive deficits. Offspring USVs influenced maternal care behaviours, but postnatal rearing did not affect cognitive development. USV trait clustering predicted adult social deficits, highlighting its potential for identifying at-risk and resilient offspring in NDDs.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 186-195"},"PeriodicalIF":8.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246521","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":"Add-on probiotics for inflammatory depression - A double-blind randomized placebo-controlled trial.","authors":"Gustav Söderberg Veibäck, Jesper Lindahl, Klara Suneson, Johanna Tjernberg, Darya Ståhl, Rikard Landberg, Marie Asp, Amanda Kjellberg, Fabian Falknäs, Klas Sjöberg, Catharina Lavebratt, Owen M Wolkowitz, Daniel Lindqvist","doi":"10.1016/j.bbi.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.06.002","url":null,"abstract":"<p><p>Previous treatment studies have suggested an antidepressant effect of adjunctive probiotics, but more high-quality Randomized Controlled Trials (RCTs) are needed before clinical implementation. The mechanisms underlying putative antidepressant effects of probiotics are not understood, but one possibility is that they are mediated via short-chain fatty acids (SCFAs) - neuroactive bacterial metabolites with anti-inflammatory properties. The main aim of this study was to test the adjunctive antidepressant efficacy of a Lactobacillus probiotic in depressed patients with concomitant systemic low-grade inflammation, and to test the relationship between treatment response and short-chain fatty acids (SCFAs) in blood and feces. In this 8-week double-blind RCT, patients with major depressive disorder (MDD), BMI ≥ 25 kg/m² and high-sensitivity C-reactive protein (hs-CRP) ≥ 1 mg/L were randomized to receive either a Limosilactobacillus reuteri (L. reuteri) probiotic supplement or placebo added to their regular and stable treatment. Primary outcomes were change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score and \"inflammatory depressive symptoms\" defined as a composite score of Patient Health Questionnaire-9 items related to sleep disturbance, energy levels, and appetite disturbance. Secondary outcomes included anxiety symptoms, anhedonia, insomnia, fatigue and gastrointestinal symptoms. SCFAs were analyzed in blood and feces pre- and post-intervention. In a modified intention-to-treat analysis including all patients with at least one post-baseline visit (n = 75), there were no significant effects of probiotics relative to placebo on any of the primary or secondary outcomes (all p > 0.25). Lower baseline levels, and a greater treatment-associated increase, of fecal formic acid was significantly associated with a decrease in MADRS score in the probiotics group (p < 0.01). While we did not observe an overall antidepressant effect of add-on L. reuteri probiotic for overweight depressed patients with systemic low-grade inflammation, we found preliminary evidence for anti-inflammatory formic acid as a biomarker, and possibly a mediator, of treatment response.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246520","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":"Sex-dependent gene expression during puberty has potential mechanistic implications for the development of major depressive disorder","authors":"Zoe Zhuoling Li ,&nbsp;Georgia Kruck ,&nbsp;Gladi Thng ,&nbsp;Corina Nagy","doi":"10.1016/j.bbi.2025.05.023","DOIUrl":"10.1016/j.bbi.2025.05.023","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) is a complex illness with heterogeneous symptom profiles, affecting 5% of the global population. Recent molecular studies across biological systems suggest that the manifestations of MDD are significantly shaped by sex. In response, this narrative review organizes up-to-date findings on sex-specific, MDD-related gene expression into multiple biological systems—primarily available from adult human and rodent studies. This adult-centric focus highlights a critical gap: when and how sex-dependent, MDD-associated gene expression patterns emerge, and contribute to adult manifestations. We identify puberty as a sensitive developmental window during which sex-dependent gene expression and regulatory patterns may emerge and carry their impacts into adulthood. We define this as a sex-specific framework established during puberty. To address the “how,” we synthesize empirical evidence on the molecular mechanisms associated with the emergence and long-term influence of this framework. Finally, we explore how perturbations acting on this framework may further bifurcate expression patterns and ultimately give rise to the sex-divergent manifestations of MDD observed in adulthood. Overall, this review positions puberty as a key developmental window and calls for future sex-stratified functional genomic studies that span the pubertal timeline.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 244-266"},"PeriodicalIF":8.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246522","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":"Pathogen-specific exposure is associated with multisite chronic pain: A prospective cohort study","authors":"Jialiu Fang ,&nbsp;Zemene Demelash Kifle ,&nbsp;Jing Tian ,&nbsp;Silvana Bettiol ,&nbsp;Flavia Cicuttini ,&nbsp;Graeme Jones ,&nbsp;Feng Pan","doi":"10.1016/j.bbi.2025.05.028","DOIUrl":"10.1016/j.bbi.2025.05.028","url":null,"abstract":"<div><div>Evidence suggests that pathogens may influence pain perception and regulation; however, no study has explored the relationship between serological evidence of infection and multisite chronic musculoskeletal pain. Therefore, this study aimed to investigate the association between serological evidence of infection and multisite chronic musculoskeletal pain. Participants (n = 6,814; mean [SD]age, 56.5[8.2] years; females [52.9 %]) in the UK Biobank were included. Multiplex serology panel measuring serum immunoglobulin G antibody levels against 20 infectious agents was performed at baseline. Chronic pain (≥3 months) in the knee, neck/shoulder, hip, back, or ‘all over the body’ was assessed at baseline and follow-up. Participants were grouped by number of chronic pain sites: no chronic pain, chronic pain in 1–2 sites, or ≥3 sites. Multinomial logistic regression and mixed-effect multinomial logistic regression models were used for the analyses. The seroprevalences of serologically detected infections across the 20 agents ranged from 0.2 % to 95.4 %. In multivariable analyses, serological evidence of infection with Epstein-Barr Virus (EBV), Human T-Cell Lymphotropic Virus Type-1 (HTLV-1), and <em>Chlamydia Trachomatis</em> was cross-sectionally associated with chronic pain in ≥3 sites compared to those without chronic pain. In longitudinal analyses, EBV [relative risk ratio (RRR) = 2.18, 95 %CI:1.17 − 4.05] and <em>Chlamydia Trachomatis</em> [RRR = 1.38, 95 %CI:1.09 − 1.74] were also associated with chronic pain in ≥3 sites. Additionally, serological evidence of single and multiple infections was associated with chronic pain in ≥3 sites, but not in 1–2 sites. Collectively, serological evidence of infection with EBV and <em>Chlamydia Trachomatis</em> is associated with multisite chronic musculoskeletal pain. These findings suggest that infectious agents may play a role in the pathogenesis of widespread chronic pain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 157-164"},"PeriodicalIF":8.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231355","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":"Nod2 deficiency exacerbates schizophrenia-related alterations in offspring of maternal immune activation in a sex-dependent manner","authors":"Fengjie Gao ,&nbsp;Chuyao Wang ,&nbsp;Zhen Cao ,&nbsp;Xinyu Zhang ,&nbsp;Wenyu Xi ,&nbsp;Yixin Liu ,&nbsp;Xianyan Zhan ,&nbsp;Min Jia ,&nbsp;Ningzhi Gou ,&nbsp;Lu Yu ,&nbsp;Yudan Zhang ,&nbsp;Yijie Guo ,&nbsp;Wei Wang ,&nbsp;Feng Zhu ,&nbsp;Xiancang Ma ,&nbsp;Yuan Gao","doi":"10.1016/j.bbi.2025.05.030","DOIUrl":"10.1016/j.bbi.2025.05.030","url":null,"abstract":"<div><h3>Introduction</h3><div>Schizophrenia is a severe mental disorder with a complex etiopathogenesis involving both genetic and environmental risk factors. Evidence suggests that immune dysregulation plays a key role in its development, with maternal immune activation (MIA) during pregnancy identified as a significant environmental contributor. However, not all maternal infections result in schizophrenia-like outcomes, indicating that genetic susceptibility may render some individuals more vulnerable to MIA. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular receptor, plays a crucial role in maintaining the balance between intestinal microbiota and immune responses, but its precise role in gut-brain interactions during neurodevelopment remain unclear.</div></div><div><h3>Methods</h3><div>To investigate the interaction between MIA and <em>Nod2</em> deficiency, we evaluated behavioral and physiological phenotypes in <em>Nod2</em>^-/- mice exposed to poly(I:C)-induced MIA. In addition to immune responses, we analyzed maternal gut microbiota and the transmission of microbiota between mothers and offspring. Given the role of the gut-brain axis in schizophrenia, we conducted intestinal immunofluorescence staining, organoid cultures, and RNA sequencing of fetal brains to assess gut injury and neuroimmune changes in the brain. Male and female offspring were analyzed separately.</div></div><div><h3>Results</h3><div>Dual exposure led to schizophrenia-like behaviors in a sex-specific manner, as well as brain development disruptions, compromised gut integrity, reduced intestinal organoid-forming capacity, and altered gut microbiota composition. Importantly, maternal gut microbiota disturbances, coupled with microbial transmission to offspring, appear to increase schizophrenia risk with potential long-term behavioral consequences.</div></div><div><h3>Conclusion</h3><div>This study underscores the intricate interplay of genetic, environmental, and microbiome factors, offering a valuable model for investigating the complex pathophysiology of neurodevelopmental disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 126-142"},"PeriodicalIF":8.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207728","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":"Commentary to the article: “Differences in inflammation among black and white individuals: A systematic review and meta-analysis”","authors":"Aura Maria Ramírez ,&nbsp;Laura Manuela Olarte Bermúdez ,&nbsp;Nelson Bedoya","doi":"10.1016/j.bbi.2025.05.029","DOIUrl":"10.1016/j.bbi.2025.05.029","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 124-125"},"PeriodicalIF":8.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207727","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":"HDAC inhibitors engage MITF and the disease-associated microglia signature to enhance amyloid β uptake","authors":"Verena Haage ,&nbsp;John F. Tuddenham ,&nbsp;Alex Bautista ,&nbsp;Frankie Garcia G. ,&nbsp;Charles C. White ,&nbsp;Ronak Patel ,&nbsp;Natacha Comandante-Lou ,&nbsp;Victoria Marshe ,&nbsp;Jennifer Griffin ,&nbsp;Ye Zhou ,&nbsp;Deniz Ghaffari ,&nbsp;Beatrice Acheson ,&nbsp;Mariko Taga ,&nbsp;Peter H. St George-Hyslop ,&nbsp;Rajesh Kumar Soni ,&nbsp;Peter A. Sims ,&nbsp;Vilas Menon ,&nbsp;Andrew A. Sproul ,&nbsp;Philip L. De Jager","doi":"10.1016/j.bbi.2025.05.027","DOIUrl":"10.1016/j.bbi.2025.05.027","url":null,"abstract":"<div><div>Disease-associated microglia (DAM), initially described in mouse models of neurodegenerative diseases, have been classified into two related states; starting from a TREM2-independent DAM1 state to a TREM2dependent state termed DAM2, with each state being characterized by the expression of specific marker genes (Keren-Shaul, 2017). Recently, single-cell (sc)RNA-Seq studies have reported the existence of DAM in humans (Pettas, 2022; Jauregui, 2023; Friedman, 2018; Mathys, 2019; Tuddenham, 2024); however, whether DAM play beneficial or detrimental roles in the context of neurodegeneration is still under debate (Butovsky and Weiner, 2018; Wang and Colonna, 2019). Here, we present a pharmacological approach to mimic human DAM <em>in vitro</em>: we validated <em>in silico</em> predictions that two different histone deacetylase (HDAC) inhibitors, Entinostat and Vorinostat, recapitulate aspects of the DAM signature in two human microglia-like model systems. HDAC inhibition increases RNA expression of <em>MITF</em>, a transcription factor previously described as a regulator of the DAM signature (Dolan, 2023). This engagement of <em>MITF</em> appears to be associated with one part of the DAM signature, refining our understanding of the DAM signature as a combination of at least two transcriptional programs that appear to be correlated <em>in vivo</em>. Further, we functionally characterized our DAM-like model system, showing that the upregulation of this transcriptional program by HDAC inhibitors leads to an upregulation of amyloid β and pHrodo Dextran uptake – while E.coli uptake is reduced – and a specific reduction of MCP1 secretion in response to IFN-γ and TNF-α. Enhanced amyloid β uptake was confirmed in iPSC-derived microglia. Overall, our strategy for compound-driven microglial polarization offers potential for exploring the function of human DAM and for an immunomodulatory strategy around HDAC inhibition.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 279-293"},"PeriodicalIF":8.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198276","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":"Plasma kynurenine pathway metabolite levels increase in depressed patients after antidepressant treatment","authors":"Romain Colle ,&nbsp;Kenneth Chappell ,&nbsp;Khalil El Asmar ,&nbsp;Bruno Fève ,&nbsp;Philippe Chanson ,&nbsp;Denis J. David ,&nbsp;Céline Verstuyft ,&nbsp;Laurent Becquemont ,&nbsp;Emmanuelle Corruble","doi":"10.1016/j.bbi.2025.05.025","DOIUrl":"10.1016/j.bbi.2025.05.025","url":null,"abstract":"<div><div>The kynurenine (KYN) pathway helps regulate physiological systems implicated in major depressive disorder (MDD). We showed that plasma levels of KYN, kynurenic acid (KA), xanthurenic acid (XA), 3-hydroxyanthranilic acid (3-HAA), and picolinic acid (PA) are lower in depressed individuals. However, whether these levels are restored following treatment with antidepressant drugs (AD) and if this restoration is associated with clinical improvement remains unclear. Fasting plasma levels of tryptophan (TRP) and these metabolites, as well as the KYN/TRP ratio, were investigated in 173 depressed patients of the METADAP cohort and 214 healthy controls of VARIETE. Measures were obtained at baseline and 3 and 6 months after beginning AD treatment. Post-treatment changes in metabolites and their associations with changes in the 17-item Hamilton Depression Rating Scale (HDRS) score were analyzed using linear mixed-effects models. Plasma metabolite levels increased following AD treatment, with significant increases in KA (<em>P_FDR</em> = 0.00014), 3-HAA (<em>P_FDR</em> = 0.034), and PA (<em>P_FDR</em> = 0.0097). The KYN/TRP ratio and KA failed to return to healthy control levels. Increases in the KYN/TRP ratio (coef = -1.08, 95 %CI [-1.92–-0.23], <em>P_FDR</em> = 0.045) and KYN levels (coef = -2.37, 95 %CI [-3.83–-0.91], <em>P_FDR</em> = 0.0011) were significantly associated with HDRS score reductions, indicating depressive symptom improvement. Altogether, we observed increases in plasma KYN pathway metabolite levels in depressed patients following 6 months of AD treatment that, for some, was significantly associated with clinical improvement. Our findings suggest increases in these metabolites may be relevant to treating depression.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 92-99"},"PeriodicalIF":8.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166989","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":"Long-term dynamics of the spinal cord injury neuroinflammatory response and sensory dysfunction in female mice","authors":"Neal J. Wrobel ,&nbsp;Quan Shen ,&nbsp;Dustin H. Kim ,&nbsp;Bahar Adavoody ,&nbsp;Daniela Garcia Prada ,&nbsp;Richard G. Fessler ,&nbsp;Brian T. David","doi":"10.1016/j.bbi.2025.05.024","DOIUrl":"10.1016/j.bbi.2025.05.024","url":null,"abstract":"<div><div>The neuroinflammatory response which takes place within the spinal cord following a traumatic spinal cord injury (SCI) is widely recognized as a major influencer of the progression and severity of the secondary tissue damage which occurs after injury onset. Immunomodulatory therapies aimed at reducing secondary injury are, therefore, a notable point of focus in SCI research. To inform future studies aimed at development of such therapies, we present a detailed characterization of the dynamics of the spinal cord neuroimmune response in mice throughout the first 6 months after contusive SCI.</div><div>Female wild type (C57BL/6) mice received moderate spinal cord contusions at T9 (<em>n</em> = 8/cohort) while control mice remained naïve (<em>n</em> = 6/cohort). Nine terminal assessment time points were included, ranging from 1 day to 6 months post-injury (each timepoint was replicated between one and four times). At each terminal time point, levels of T cells, helper T cells, cytotoxic T cells, regulatory T cells, macrophages, and microglia within the spinal cord were assessed via flow cytometry. Measures of locomotor (open-field task) and sensory (tail flick) function were used to assess behavioral recovery.</div><div>The spinal cord neuroimmune response in mice exhibited a biphasic pattern, with one peak of peripheral immune cell infiltration within the first 2 weeks post-injury, followed by a second peak at 2 months post-injury. Both T cells and macrophages remained elevated in injured spinal cords, relative to controls, at 6 months post-injury. Spinal cord inflammation correlated with exacerbated sensory impairment acutely but correlated with greater normalization of sensory function at 6 months post-injury. Higher inflammation at 6 months post-injury was also associated with an increase in spleen to body mass ratio.</div><div>Together, the results of this investigation highlight the persistent nature of the SCI neuroinflammatory response and indicate that its relationship to other bodily systems continues to evolve even in the late-chronic stage of injury.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 143-156"},"PeriodicalIF":8.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180251","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}