Brain, Behavior, and Immunity最新文献

{"title":"Reevaluating feature importances in machine learning models for schizophrenia and bipolar disorder: The need for true associations","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.bbi.2024.11.036","DOIUrl":"10.1016/j.bbi.2024.11.036","url":null,"abstract":"<div><div>Skorobogatov et al. developed supervised machine learning models to predict diagnoses and illness states in schizophrenia and bipolar disorder. However, their reliance on bootstrap forests and generalized regressions introduces significant biases in feature importance assessments. This paper highlights the critical distinction between feature importances generated by machine learning and actual associations, which are often model-specific and context-dependent. We underscore the limitations of biased feature importances and advocate for the use of robust statistical methods, such as Chi-squared tests and Spearman’s correlation, to reveal true associations. Reassessing findings with these methods will enable more accurate interpretations and reinforce the importance of understanding the limitations inherent in machine learning methodologies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 123-124"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766338","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":"Neonatal exposure to morphine results in prolonged pain hypersensitivity during adolescence, driven by gut microbial dysbiosis and gut-brain axis-mediated inflammation","authors":"Danielle Antoine ,&nbsp;Junyi Tao ,&nbsp;Salma Singh ,&nbsp;Praveen Kumar Singh ,&nbsp;Barbara G Marin ,&nbsp;Sabita Roy","doi":"10.1016/j.bbi.2025.01.021","DOIUrl":"10.1016/j.bbi.2025.01.021","url":null,"abstract":"<div><div>Opioids, such as morphine, are used in the Neonatal Intensive Care Unit (NICU) for pain relief in neonates. However, the available evidence concerning the benefits and harms of opioid therapy in neonates remains limited. While previous studies have reported that neonatal morphine exposure (NME) results in long-term heightened pain sensitivity, the underlying mechanisms are not well understood. This study proposes that dysbiosis of the gut microbiome contributes to pain hypersensitivity following NME. Using an adolescent female murine model, pain sensitivity was evaluated using the tail flick and hot plate assays for thermal pain and the Von Frey assay for mechanical pain. Gut microbiome composition was assessed using 16S rRNA sequencing, while transcriptomic changes in midbrain samples were investigated using bulk RNA sequencing. NME induced prolonged hypersensitivity to thermal and mechanical pain in adolescence, accompanied by persistent gut microbial dysbiosis and sustained systemic inflammation, characterized by elevated circulating cytokine levels (e.g., IL-1α, IL-12p70, IFN-γ, IL-10). Transplantation of the microbiome from NME adolescents recapitulated pain hypersensitivity in naïve adolescent mice, while neonatal probiotic intervention with <em>Bifidobacterium infantis</em> (<em>B. infantis</em>) reversed the pain hypersensitivity by preventing gut dysbiosis and associated systemic inflammation. Furthermore, transcriptomic analysis of midbrain tissues revealed that NME upregulated several genes and key signaling pathways, including those related to immune activation and excitatory signaling, which were notably mitigated with neonatal <em>B. infantis</em> administration. Together, these findings highlight the critical role of the gut-brain axis in modulating pain sensitivity and suggest that targeting the gut microbiome offers a promising therapeutic strategy for managing neurobiological disorders following early opioid exposure.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 3-23"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122211","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":"GDF15-GFRAL signaling drives weight loss and lipid metabolism in mouse model of amyotrophic lateral sclerosis","authors":"Germana Cocozza ,&nbsp;Ludovica Maria Busdraghi ,&nbsp;Giuseppina Chece ,&nbsp;Antonio Menini ,&nbsp;Marco Ceccanti ,&nbsp;Laura Libonati ,&nbsp;Chiara Cambieri ,&nbsp;Francesco Fiorentino ,&nbsp;Dante Rotili ,&nbsp;Ferdinando Scavizzi ,&nbsp;Marcello Raspa ,&nbsp;Eleonora Aronica ,&nbsp;Maurizio Inghilleri ,&nbsp;Stefano Garofalo ,&nbsp;Cristina Limatola","doi":"10.1016/j.bbi.2024.12.010","DOIUrl":"10.1016/j.bbi.2024.12.010","url":null,"abstract":"<div><div>Weight loss is a common early sign in amyotrophic lateral sclerosis (ALS) patients and negatively correlates with survival. In different cancers and metabolic disorders, high levels of serum growth differentiation factor 15 (GDF15) contribute to a decrease of food intake and body weight, acting through GDNF family receptor alpha-like (GFRAL). Here we report that GDF15 is highly expressed in the peripheral blood of ALS patients and in the hSOD1^G93A mouse model and that GFRAL is upregulated in the brainstem of hSOD1^G93A mice. We demonstrate that the localized GFRAL silencing by shRNA in the area postrema/nucleus tractus solitarius of hSOD1^G93A mice induces weight gain, reduces adipose tissue wasting, ameliorates the motor function and muscle atrophy and prolongs the survival time. We report that microglial cells could be involved in mediating these effects because their depletion with PLX5622 reduces brainstem GDF15 expression, weight loss and the expression of lipolytic genes in adipose tissue. Altogether these results reveal a key role of GDF15-GFRAL signaling in regulating weight loss and the alteration of and lipid metabolism in the early phases of ALS.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 280-293"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821789","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":"Preventive application of probiotics in ischemic stroke therapy through the gut-spleen-brain axis","authors":"Liqi Li","doi":"10.1016/j.bbi.2024.12.014","DOIUrl":"10.1016/j.bbi.2024.12.014","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Page 294"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823742","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":"Ezrin-mediated astrocyte-synapse signaling regulates cognitive function via astrocyte morphological changes in fine processes in male mice","authors":"Lingmin Chen ,&nbsp;Jiao Jiao ,&nbsp;Fan Lei ,&nbsp;Bin Zhou ,&nbsp;Hong Li ,&nbsp;Ping Liao ,&nbsp;Xin Li ,&nbsp;Yi Kang ,&nbsp;Jin Liu ,&nbsp;Ruotian Jiang","doi":"10.1016/j.bbi.2024.11.022","DOIUrl":"10.1016/j.bbi.2024.11.022","url":null,"abstract":"<div><div>Astrocytes, which actively participate in cognitive processes, have a complex spongiform morphology, highlighted by extensive ramified fine processes that closely enwrap the pre- and post-synaptic compartments, forming tripartite synapses. However, the role of astrocyte morphology in cognitive processes remains incompletely understood and even controversial. The actin-binding protein Ezrin is highly expressed in astrocytes and is a key structural determinant of astrocyte morphology. Here, we found that Ezrin expression and astrocyte fine process volume in the hippocampus of male mice increased after learning but decreased after lipopolysaccharide injection and in a mouse model of postoperative cognitive dysfunction, both of which involved models with impaired cognitive function. Additionally, astrocytic Ezrin knock-out led to significantly decreased astrocytic fine process volumes, decreased astrocyte-neuron proximity, and induced anxiety-like behaviors and cognitive dysfunction. Astrocytic Ezrin deficiency in the hippocampus was achieved by using a microRNA silencing technique delivered by adeno-associated viruses. Down-regulation of Ezrin in hippocampal astrocytes led to disrupted astrocyte-synapse interactions and impaired synaptic functions, including synaptic transmission and synaptic plasticity, which could be rescued by exogenous administration of D-serine. Remarkably, decreased Ezrin expression and reduced astrocyte fine processes volumes were also observed in aged mice with decreased cognitive function. Moreover, overexpression of astrocytic Ezrin increased astrocyte fine process volumes and improved cognitive function in aged mice. Overall, our results indicate Ezrin-mediated astrocyte fine processes integrity shapes astrocyte-synapse signaling contributing to cognitive function.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 177-191"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695089","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":"Sick and detached: Does experimental inflammation impact on movement synchrony in humans?","authors":"Vera Flasbeck ,&nbsp;Fabian T. Ramseyer ,&nbsp;Manfred Schedlowski ,&nbsp;Harald Engler ,&nbsp;Martin Brüne","doi":"10.1016/j.bbi.2024.11.028","DOIUrl":"10.1016/j.bbi.2024.11.028","url":null,"abstract":"<div><div>Interpersonal connectedness is a central feature of human interaction that can be compromised during illness. Nonverbal signals play a crucial role in this context, and humans, like other animals, have evolved a behavioral immune system that enables individuals to detect subtle cues of sickness in others. Conversely, sick individuals often tend to avoid social interaction, a key component of sickness behavior. The coordination of body movements between two individuals (movement synchrony) is a measure of the quality of relationships that could provide insights into an interlocutor’s sickness state. In the present study, we explored the effect of lipopolysaccharide (LPS) administration, a naturalistic stimulus for inflammation-induced sickness, on movement synchrony in healthy volunteers randomly assigned to a double-blind interview with a non-treated interviewer conducted 2.5 h after intravenous injection of either LPS (N = 26) or placebo (N = 25). Movement synchrony was assessed by automated video analysis of subject’s and interviewer’s head movements. Lagged cross-correlations were used to objectively quantify coordination in dyads and to assess patterns of temporal movement synchronization. Data analysis revealed that dyads with subjects under placebo displayed a pattern of movement coordination comparable to that seen in previous studies. However, dyads with subjects under LPS showed a loss of simultaneous movement (i.e. moving at the same time) with the interview partner, which is normally the temporal domain providing the highest level of synchrony. Together, the findings suggest that immediate social interaction is attenuated when one interlocutor is exposed to systemic inflammation, while the other is unaffected. This effect can be attributed to both sickness behavior on one hand and correlates of the behavioral immune system on the other hand.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 157-162"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754699","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":"Plasma levels of matrix metalloproteinases in early psychosis, anxiety and depression: Evidence from the ALSPAC cohort","authors":"Lorenzo Ghelfi ,&nbsp;David Mongan ,&nbsp;Subash Raj Susai ,&nbsp;Melanie Föcking ,&nbsp;David R. Cotter ,&nbsp;Mary Cannon","doi":"10.1016/j.bbi.2024.11.035","DOIUrl":"10.1016/j.bbi.2024.11.035","url":null,"abstract":"<div><h3>Background</h3><div>Converging evidence supports the role of Matrix Metalloproteinases (MMPs) in psychiatric disorders. Originally identified as regulators of the extracellular matrix (ECM), MMPs’ functions span multiple processes, including inflammation, synaptic plasticity, neuronal migration, and blood–brain barrier maintenance. Tissue Inhibitors of Metalloproteinases (TIMPs) are major regulators of MMPs. In the present study we examined the associations of plasma MMPs and TIMPs with mental disorders in young adults aged 24 years in the Avon Longitudinal Study of Parents and Children (ALSPAC).</div></div><div><h3>Methods</h3><div>The present study was a nested case control study within the Avon Longitudinal Study of Parents and Children and comprised 374 participants who met criteria for psychiatric disorders (35 met the criteria for psychotic disorder, 201 for mild/moderate depressive disorder, and 266 for generalised anxiety disorder) and 401 controls. All cases and controls had were selected from the group of 4019 participants who had attended at age 24 years, completed psychiatric assessments and provided plasma samples. Plasma concentrations of MMP2, MMP3, MMP9 and TIMP-4 were quantified using proximity extension assays available on Olink® Cardiovascular Panel III. Logistic regression analysis compared standardised MMPs and TIMPs levels in cases and controls. Models were adjusted for sex, body mass index, and cigarette smoking.</div></div><div><h3>Results</h3><div>There was evidence for an association between MMP3 and depressive disorder (Odds ratio [OR] 1.35, 95 % confidence interval [CI] 1.06–1.73). There was evidence for an association between TIMP4 and depressive disorder (OR 1.51, 95 % CI 1.22–1.88) and generalised anxiety disorder (OR 1.43, 95 % CI 1.19–1.72). There was no evidence for an association between MMPs and psychotic disorders.</div></div><div><h3>Conclusions</h3><div>The study revealed that 24-year-olds with depressive and anxiety disorders exhibited elevated plasma concentrations of TIMP-4 compared to controls. There was evidence for an association between MMP3 and depressive disorder. These findings provide further support for the involvement of metalloproteinases as biomarkers in the pathophysiology of mental disorders during early adulthood.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 137-143"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766329","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":"Blood Biomarker Signatures for Slow Gait Speed in Older Adults: An Explainable Machine Learning Approach","authors":"Evrim Gökçe ,&nbsp;Thomas Freret,&nbsp;Antoine Langeard","doi":"10.1016/j.bbi.2024.12.007","DOIUrl":"10.1016/j.bbi.2024.12.007","url":null,"abstract":"<div><div>Maintaining physical function is crucial for independent living in older adults, with gait speed being a key predictor of health outcomes. Blood biomarkers may potentially monitor older adults’ mobility, yet their association with slow gait speed still needs to be explored. This study aimed to investigate the relationship between blood biomarkers and gait speed using the Midlife in the United States (MIDUS) study biomarker dataset. A cross-sectional design was employed for analysis, involving 405 individuals aged 60 years and over. We used a machine learning framework, specifically the XGBoost algorithm, feature selection methods, and the Shapley Additive Explanations, to develop an explainable prediction model for slow gait speed. Our model demonstrated the highest cross-validation score with the six most important features among 35 variables, as elevated interleukin-6, C-reactive protein, glycosylated hemoglobin, interleukin-8, older age, and female sex were significantly associated with reduced gait speed (area under the curve = 0.75). Our findings suggest that blood biomarkers can play a critical role in integrated models to assess and monitor slow gait speed in older adults. Identifying key blood biomarkers provides valuable insights into the underlying physiological mechanisms of mobility decline and offers promising avenues for early intervention to preserve mobility in the aging population.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 295-304"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From feather pecking to immunity: Immune differences between lines selected for high and low feather pecking","authors":"Tanja Hofmann ,&nbsp;Sonja Schmucker ,&nbsp;Werner Bessei ,&nbsp;Volker Stefanski","doi":"10.1016/j.bbi.2024.12.009","DOIUrl":"10.1016/j.bbi.2024.12.009","url":null,"abstract":"<div><div>Feather pecking (FP) is a serious behavioral disorder in laying hens, leading to feather damage, skin lesions, and often resulting in cannibalism. The mechanisms underlying FP are not clear yet, but recently the role of the immune system as a cause has been discussed. In humans, the interrelation between personality traits and the immune system is well-documented, with impulsivity and hyperactivity linked to distinct alterations in blood immune cell numbers and to elevated levels of pro-inflammatory cytokines. Similarly, FP in hens is associated with impulsivity and hyperactivity, suggesting a possible connection between FP and immune cell alterations. In this study numbers of leukocyte subsets in blood, spleen and cecal tonsils, along with mitogen-induced lymphocyte proliferative response and antibody concentrations across hens selectively bred for high (HFP) and low (LFP) feather pecking behavior were analyzed. Results showed that divergent selection altered FP behavior, with HFP hens showing about 10 times more pecking behavior than hens of the LFP line. HFP hens had lower numbers of T helper cells, CD4+ CD25^high as well as B cells compared to LFP hens. Furthermore, HFP hens demonstrated a stronger proliferation of T cells when stimulated with ConA, while showed a weaker response in T cell-dependent B cell proliferation when stimulated with PWM, compared to LFP hens. Antibody plasma concentrations were similar between both lines. These findings highlight substantial immunological differences between HFP and LFP hens, especially in T cell immunity, and support the hypothesis that FP may be an immune-related behavioral response.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages 253-263"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PNIRS Society Announcements","authors":"","doi":"10.1016/S0889-1591(25)00009-1","DOIUrl":"10.1016/S0889-1591(25)00009-1","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"124 ","pages":"Pages iv-v"},"PeriodicalIF":8.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143094703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}