Brain, Behavior, and Immunity最新文献

{"title":"Discovery of novel blood–brain barrier neuropathology in schizophrenia and bipolar disorder midbrain","authors":"Yunting Zhu ,&nbsp;Gerardo Mendez Victoriano ,&nbsp;Maree J Webster ,&nbsp;Frank A. Middleton ,&nbsp;Paul T. Massa ,&nbsp;Christine Fuller ,&nbsp;Cynthia Shannon Weickert","doi":"10.1016/j.bbi.2026.106292","DOIUrl":"10.1016/j.bbi.2026.106292","url":null,"abstract":"<div><div>Elevated pro-inflammatory cytokines and increased macrophage densities have been found in ∼ 35–50 % of schizophrenia and bipolar disorder brains. However, the influence of neuroinflammation on the blood–brain barrier (BBB) in these serious mental illnesses remains unclear. Here, we measured and compared multiple BBB-associated molecules in the ventral midbrain, including chemokines, macrophage markers, adhesion molecules, tight junction proteins, and basement membrane proteins in people with schizophrenia (n = 35), or bipolar disorder (n = 34), and controls (n = 33), stratified by inflammatory status. Both mRNA and protein levels of macrophage chemokine (CCL2) and macrophage scavenger receptor (CD163) were significantly elevated in the neuroinflammatory schizophrenia (high) compared to all the low inflammatory subgroups. Adhesion molecule mRNAs (ICAM1 and PECAM1) were increased in both schizophrenia and bipolar disorder high inflammatory subgroups, but PECAM1 protein was only elevated in schizophrenia, while ICAM1 protein was decreased in bipolar disorder. We found lower collagen IV (ColIV) protein levels in bipolar disorder. Tight junction protein claudin-5 (CLDN5) mRNA was elevated in both schizophrenia and bipolar disorder high inflammatory subgroups, while occludin (OCLN) mRNA was decreased in schizophrenia, especially in the high inflammatory subgroup. CLDN5 immunostaining revealed increased fragmented blood vessels with bursts of CLDN5 + processes surrounding and appearing to emanate from endothelial cells in schizophrenia and bipolar disorder high inflammation subgroup. Collectively, the high inflammatory individuals in both schizophrenia and/or bipolar disorder display more signs of BBB alterations, including increased macrophage chemoattraction, changed adhesion molecules, and altered tight junction proteins, though they have distinct molecular signatures of BBB pathology in the midbrain.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106292"},"PeriodicalIF":7.6,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008993","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":"Post-infection mental illness: Mapping pathways of vulnerability and resilience in VIRAL-MInds","authors":"Eva Wachtelaer ,&nbsp;Chloë Trippaers ,&nbsp;Ole A. Andreassen ,&nbsp;Ingrid Torp Johansen ,&nbsp;Nils Eiel Steen ,&nbsp;Helga Ask ,&nbsp;Dana Tzur Bitan ,&nbsp;Amit Kramer ,&nbsp;Sara Poletti ,&nbsp;Federica Colombo ,&nbsp;Livia De Picker","doi":"10.1016/j.bbi.2026.106291","DOIUrl":"10.1016/j.bbi.2026.106291","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106291"},"PeriodicalIF":7.6,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemogenetic activation of oxytocinergic neurons modulates acute neuroinflammation and improves brain development after pediatric traumatic brain injury","authors":"Marit Knoop ,&nbsp;Ece Trak ,&nbsp;Marie-Laure Possovre ,&nbsp;Yohan van de Looij ,&nbsp;Gabriel Schirmbeck ,&nbsp;Kelly Ceyzériat ,&nbsp;Jean-Luc Pitetti ,&nbsp;Eduardo Sanches ,&nbsp;Stefano Musardo ,&nbsp;Philippe Millet ,&nbsp;Stergios Tsartsalis ,&nbsp;Benjamin B. Tournier ,&nbsp;Camilla Bellone ,&nbsp;Stéphane V. Sizonenko ,&nbsp;Alice Jacquens ,&nbsp;Olivier Baud","doi":"10.1016/j.bbi.2026.106293","DOIUrl":"10.1016/j.bbi.2026.106293","url":null,"abstract":"<div><div><u>Objective</u>: Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in infants, whose neurodevelopmental consequences currently lack effective treatment. Since TBI is associated with neuroinflammation, modulation of the post-injury neuroinflammatory response is a promising strategy. Oxytocin is suggested to possess anti-inflammatory properties, and seems to play a role in clinical interventions that improve brain development in neonates. However, the underlying mechanisms remain unclear, as does its applicability to acute brain injury.</div><div><u>Methods</u>: Here, we assess the effects of chemogenetic activation of oxytocinergic neurons on acute neuroinflammation and on long-term brain development after TBI in postnatal day 7 (P7) male mice. Immunohistochemistry, RNA sequencing, <em>ex-vivo</em> MRI-diffusion tensor imaging, <em>in-vivo</em> functional ultrasound imaging and behavioral assays are used for assessment. Oxytocinergic neurons were chemogenetically activated daily between P7 and P10.</div><div><u>Results</u>: We show that chemogenetic activation of oxytocinergic neurons mitigates the acute neuroinflammatory response to TBI 24 h post-injury, where it reduces the expression of inflammation-related genes, and promotes brain repair and development gene pathways in microglia. In the long-term, early-life oxytocinergic neuron activation improves subcortical and cortical white matter damage after TBI, prevents hyperactivity and loss of social behavior, and restores TBI-induced alterations in resting-state functional connectivity of the isocortex. These effects were found 35 days after the last treatment session.</div><div><u>Conclusions</u>: Our findings enhance the understanding of neuroinflammation modulation by oxytocin, reveal its long-term effects, and support intervention associated with endogenous oxytocin release as a promising neuroprotective strategy in pediatric TBI.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106293"},"PeriodicalIF":7.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997320","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":"Midbrain microglial and macrophage mRNAs distinguish neuroinflammatory schizophrenia from bipolar disorder","authors":"Gerardo Mendez-Victoriano ,&nbsp;Yunting Zhu ,&nbsp;Yasmine Kostoglou ,&nbsp;Adam K. Walker ,&nbsp;Frank Middleton ,&nbsp;Paul T. Massa ,&nbsp;Bart J.L. Eggen ,&nbsp;Maree J. Webster ,&nbsp;Iris E.C. Sommer ,&nbsp;Cynthia S. Weickert","doi":"10.1016/j.bbi.2026.106276","DOIUrl":"10.1016/j.bbi.2026.106276","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Increased microglial/macrophage transcripts are found in the midbrains of people with a neuroinflammatory subtype of schizophrenia. However, it is unknown in which immune cell population these transcripts are mostly expressed, nor do we know if transcriptional changes in microglial/macrophage markers are also found in the midbrain of neuroinflammatory bipolar disorder.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Here, we determined the extent of microglial/macrophage changes in the ventral midbrain (at the level of the oculomotor nerve exit) of a large cohort of people with schizophrenia and bipolar disorder, defined as either low or high-inflammation, compared to controls. We aimed to confirm in which cell-type cluster our transcripts were expressed (microglia vs macrophages). First, we mapped the cellular expression of putative microglial/macrophage markers via snRNA-seq. Then, mRNA levels of 11 microglial/macrophage markers were measured and compared via RT-PCR from human post-mortem midbrains of 61 healthy controls, 63 schizophrenia cases, and 33 bipolar disorder cases.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;7/11 mRNAs (&lt;em&gt;IBA1&lt;/em&gt;, &lt;em&gt;CD11B&lt;/em&gt;, &lt;em&gt;CX3CR1&lt;/em&gt;, &lt;em&gt;P2RY12&lt;/em&gt;, &lt;em&gt;CD64&lt;/em&gt;, &lt;em&gt;CD40&lt;/em&gt;, &amp; &lt;em&gt;TMEM119&lt;/em&gt;) were mainly expressed in microglial cell clusters; 2 mRNAs were in the macrophage cell cluster (&lt;em&gt;CD32C, CD86&lt;/em&gt;); 1 mRNA was broadly expressed (&lt;em&gt;HEXB&lt;/em&gt;), and &lt;em&gt;CD68&lt;/em&gt; mRNA was too low to confirm cellular source by snRNA-seq. Across groups, transcripts associated with microglia activation and motility were significantly increased in high-inflammation schizophrenia (&lt;em&gt;IBA1, CD11B&lt;/em&gt;; all &lt;em&gt;p&lt;/em&gt; ≤ 0.001) and significantly decreased in high-inflammation bipolar disorder (&lt;em&gt;P2RY12&lt;/em&gt;, &lt;em&gt;CX3CR1&lt;/em&gt;; all &lt;em&gt;p&lt;/em&gt; ≤ 0.01) compared to low-inflammation controls. Transcripts associated with microglial and macrophage activation via FcγR-IgG/Immune complex antigen binding were significantly increased in high-inflammatory schizophrenia (&lt;em&gt;CD64&lt;/em&gt; &amp; &lt;em&gt;CD32C&lt;/em&gt;) and high-inflammatory bipolar disorder (&lt;em&gt;CD32C&lt;/em&gt;) (all &lt;em&gt;p&lt;/em&gt; ≤ 0.01). Transcripts associated with increased cytokine response (&lt;em&gt;CD40 &amp; CD86&lt;/em&gt;) and phagocytosis (&lt;em&gt;CD68&lt;/em&gt;) were significantly increased in high-inflammatory schizophrenia and divergently changed in high-inflammatory bipolar disorder (&lt;em&gt;CD40&lt;/em&gt; increased&lt;em&gt;/CD86&lt;/em&gt; decreased) (all &lt;em&gt;p&lt;/em&gt; ≤ 0.05). Overall, the number of CD68 + cells with reactive-like morphology was increased in high-inflammation schizophrenia compared to all the low-inflammation groups (all p ≤ 0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our findings strengthen the contention that microglia and macrophages are activated in schizophrenia and disrupted in bipolar disorder midbrains of high-inflammatory subgroups. This suggests that optimal immune-based treatments targeting schizophrenia and bipolar disorder patients may differ when restor","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106276"},"PeriodicalIF":7.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997279","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":"Altered gene expression associated with postoperative delirium in patients undergoing surgery and anesthesia","authors":"Maria Heinrich ,&nbsp;Anna-Rosa Krüger ,&nbsp;Sreyoshi Chatterjee ,&nbsp;Anna Fournier ,&nbsp;Florian Lammers-Lietz ,&nbsp;Roland Krause ,&nbsp;Peter Nürnberg ,&nbsp;Reinhard Schneider ,&nbsp;Georg Winterer ,&nbsp;Maik Pietzner ,&nbsp;Claudia Spies","doi":"10.1016/j.bbi.2026.106283","DOIUrl":"10.1016/j.bbi.2026.106283","url":null,"abstract":"<div><div>Postoperative delirium is a severe complication associated with poor overall and especially neurocognitive prognosis after anesthesia and surgery. As a systemic phenomenon, peripheral immune response to surgical trauma may play a central role. Although analysis of differential gene expression in peripheral immune cells could provide insights into immune dysregulation in postoperative delirium (POD), no sufficiently powered prospective cohort study has yet been conducted.</div><div>We performed gene expression analysis in N = 599 cognitively healthy male and female patients ≥65 years who provided blood samples for microarray-based gene-expression data before major elective surgery and on the first postoperative day. Patients were followed up for delirium until the seventh postoperative day. We identified differentially expressed genes in POD using a multivariable linear regression framework adjusted for sex, age, body mass index, preoperative physical status, duration of anesthesia and operative procedure.</div><div>Preoperative gene expression did not differ significantly in patients who were later diagnosed with POD. However, we identified a total of 1,063 unique significantly associated genes which differed in baseline-corrected mRNA abundance among POD patients after surgery (n = 394 upregulated, n = 681 downregulated). This set was significantly enriched for genes related to cellular and humoral immune response, RNA metabolism and platelet function.</div><div>Post-, but not preoperative gene expression in peripheral immune cells has been found to be altered in patients with POD. Whereas most enriched pathways were related to immune response and acute phase reaction, few molecular alterations were found, which may reflect nervous system alterations and warrant further investigation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106283"},"PeriodicalIF":7.6,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988364","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":"Cytokines, Somatosensory Functioning, and Psychological Distress in Post-Breast Cancer Surgery Pain: A longitudinal study.","authors":"De Groote Amber, Meeus Mira, Coppens Lenny, Kumar-Singh Samir, Dams Lore, Mosselmans Jade, Tjalma Wiebren, De Groef An, Mertens Michel Gcam","doi":"10.1016/j.bbi.2026.106281","DOIUrl":"https://doi.org/10.1016/j.bbi.2026.106281","url":null,"abstract":"<p><p>Approximately 40% of breast cancer (BC) patients experience pain during a curative treatment episode. While the biological impact of surgery and adjuvant therapies is central to pain onset, patients' pain intensity and persistence are further shaped by its interplay with psychosocial factors. Here we explored cytokine levels, somatosensory functioning, and psychological distress as biomarkers for pain in BC patients at one and three months post-surgery. Specifically, we compared these factors in BC patients with and without pain at both time points and examined their associations with pain intensity and their change over time (delta pain). Thirty-seven BC patients were measured at one and three months post-surgery. Pain intensity was assessed using the Visual Analogue Scale. Fifty-six cytokines were measured using a multiplex electrochemiluminescence-based immunoassay, somatosensory functioning through quantitative sensory testing, including thermal detection and pain thresholds, conditioned pain modulation, and temporal summation, and psychological distress (i.e., pain catastrophizing, depression, anxiety, stress, resilience, positive and negative affect) using validated questionnaires. Group comparisons and correlation analyses were conducted between these biopsychosocial factors and (delta) pain intensity. Patients in the pain group displayed higher warmth detection thresholds at the tibialis anterior muscle at both time points. At three months post-surgery, nine cytokines, anxiety and pain catastrophizing were elevated in the pain group. Correlation analysis showed that seven out of the nine elevated cytokines and anxiety positively correlated with pain intensity at three months post-surgery, supporting their potential as candidate biomarkers. Furthermore, Interleukin (IL)-17f, IL-22, IL-33, and granulocyte colony-stimulating factor (at one month) and C-reactive protein (at three months post-surgery) were positively correlated with delta pain intensity. Our findings support novel cytokine candidates for future research.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":"106281"},"PeriodicalIF":7.6,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988335","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":"Chronic constriction of the sciatic nerve does not induce mood-related comorbidities in female mice","authors":"Marion Gaborit ,&nbsp;Quentin Leboulleux ,&nbsp;Noemie Willem ,&nbsp;Coline Sagot ,&nbsp;Stephane Doridot ,&nbsp;Karin Herbeaux ,&nbsp;Melanie Kremer ,&nbsp;Amandine Bery ,&nbsp;Katia Befort ,&nbsp;Dominique Massotte","doi":"10.1016/j.bbi.2026.106286","DOIUrl":"10.1016/j.bbi.2026.106286","url":null,"abstract":"<div><h3>Background</h3><div>Neuropathic pain affects around 7–8% of the population and is associated with a high level of lifetime anxio-depressive comorbidities. Despite the higher incidence of the pathology in women, preclinical studies using rodents almost exclusively focused on males so far.</div></div><div><h3>Methods</h3><div>Sciatic nerve cuffing is a well-characterized model of neuropathy in which anxio-depressive comorbidities develop over time in male mice. In order to examine potential sex-differences in this model, we compared the alterations in the mechanical sensitivity using von Frey testing and used three ethologically relevant tests to explore their well-being (nest building), social behaviour (dyadic social interaction), and depression-like state (splash test) seven weeks after surgery. We also examined sex-related differences in neuroinflammation by quantifying changes in cytokine expression in the brainstem, a region critically involved in descending pain modulation.</div></div><div><h3>Results/conclusion</h3><div>Both male and female mice developed mechanical hypersensitivity following cuff surgery. However, no alteration in nest building ability, social dyadic interaction or grooming activity was observed in female mice seven weeks after surgery. Our data therefore suggest sex differences in the development of comorbidities associated with mechanical hypersensitivity. In addition, we evidenced in the brainstem sex-related differences in the expression of cytokines relevant to human neuropathy. Altogether, these results emphasize the need for additional comparisons between males and females to better grasp the role of neuroinflammation in pain sensitization and associated comorbidities.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106286"},"PeriodicalIF":7.6,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988410","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":"Neural mechanisms of mindfulness: reduced neural reactivity to social-evaluative threat accounts for mindfulness intervention effects on inflammatory gene expression","authors":"R.B. Blades ,&nbsp;C.C. Boyle ,&nbsp;N.I. Eisenberger ,&nbsp;S.W. Cole ,&nbsp;J.R.T. Korecki ,&nbsp;A.J. Fuligni ,&nbsp;J.E. Bower","doi":"10.1016/j.bbi.2026.106284","DOIUrl":"10.1016/j.bbi.2026.106284","url":null,"abstract":"<div><div>Mindful awareness redirects attention toward the present moment, which may reduce threat-related neural activity and downstream inflammation in response to stress. Social-evaluative threat, where the self is negatively judged by others, is a stressor with potent inflammatory consequences. As part of a randomized controlled trial (NCT05304052), the current study tested whether a mindfulness intervention reduced neural reactivity to social-evaluative threat and reduced downstream pro-inflammatory signaling. Healthy young adults were randomly assigned to a waitlist control group (n = 23) or a 6-week mindfulness intervention (Mindful Awareness Practices; MAPs; n = 26) that has previously been shown to reduce stress and inflammation. Pre- and post-intervention, we collected blood samples and BOLD neuroimaging data during a social-evaluative threat task (modified Montreal Imaging Stress Task; MIST), focusing on activity in three threat-related neural regions: amygdala, dorsal anterior cingulate cortex, and anterior insula. Leukocyte genome-wide RNA profiles were analyzed using promoter-based bioinformatic analyses to infer NF-κB transcription factor activity, a canonical pro-inflammatory signaling pathway. Relative to waitlist control, the MAPs intervention led to reductions in neural threat reactivity. MAPs also reduced NF-κB activity relative to the control condition, and this effect was no longer significant when controlling for changes in neural threat reactivity. Results suggest that reductions in threat-related neural activity may contribute to the beneficial effects of mindfulness on inflammation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106284"},"PeriodicalIF":7.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973184","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":"BMP7 alleviates trigeminal neuralgia by suppressing oxidative stress and activation of satellite glial cells via the NRF2/HO-1 pathway","authors":"Meiqin Li ,&nbsp;Gaopeng Guan ,&nbsp;Xin Li ,&nbsp;Dingquan Zou ,&nbsp;Wei Zhang ,&nbsp;Kai Chen ,&nbsp;Yanying Xiao ,&nbsp;Yaping Wang ,&nbsp;Meng Wang","doi":"10.1016/j.bbi.2026.106277","DOIUrl":"10.1016/j.bbi.2026.106277","url":null,"abstract":"<div><h3>Background</h3><div>The trigeminal ganglion (TG) is a central hub for craniofacial injurious messaging, and its abnormal function is closely related to the pathogenesis of trigeminal neuralgia (TN). Bone morphogenetic protein 7 (BMP7), a pleiotropic cytokine with both neuroprotective and anti-inflammatory effects, has been shown to have therapeutic potential for neuropathic pain (NP) and neurodegenerative diseases. However, it remains to be elucidated whether BMP7 is involved in the pathological process of TN through the regulation of TG.</div></div><div><h3>Objective</h3><div>This study aimed to investigate whether BMP7 alleviates TN by modulating oxidative stress and activation in satellite glial cells (SGCs) of the TG.</div></div><div><h3>Methods</h3><div>A rat model of TN was established by chronic constriction injury of the distal infraorbital nerve (CCI-dION). Primary rat SGCs were activated with IL-1β to create an <em>in vitro</em> model. The role of BMP7 in regulating oxidative stress was assessed through <em>in vivo</em> knockdown and <em>in vitro</em> overexpression experiments. The NRF2 inhibitor ML385 was employed to validate the essential role of the NRF2/HO-1 pathway in BMP7-mediated SGC functional modulation.</div></div><div><h3>Results</h3><div>Following successful CCI-dION model establishment, TN rats showed significantly reduced mechanical pain thresholds, aggravated cold allodynia, and increased spontaneous pain behaviors, accompanied by decreased BMP7 expression, enhanced SGC activation, and elevated ROS levels in TG. These pathological phenotypes were consistently reproduced in BMP7-knockdown rats. In IL-1β-stimulated SGCs, BMP7 silencing mimicked pathological changes, while BMP7 overexpression reversed IL-1β effects − a rescue blocked by ML385. Critically, <em>in vivo</em> BMP7 overexpression attenuated CCI-dION-induced pain, oxidative stress, and SGC activation.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that BMP7 alleviates TN by suppressing oxidative stress and activation of SGCs through activation of the NRF2/HO-1 pathway, highlighting its therapeutic potential for TN treatment.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"134 ","pages":"Article 106277"},"PeriodicalIF":7.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984470","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":"Symptomatology of depression and onset of cardiometabolic diseases − A 7-year follow-up study","authors":"Tahani Alshehri ,&nbsp;Yumeng Tian ,&nbsp;Ruifang Li-Gao ,&nbsp;Jeroen van der Velde ,&nbsp;Saskia le Cessie ,&nbsp;Frits R. Rosendaal ,&nbsp;Brenda W.J.H. Penninx ,&nbsp;Yuri Milaneschi ,&nbsp;Dennis O. Mook-Kanamori","doi":"10.1016/j.bbi.2026.106285","DOIUrl":"10.1016/j.bbi.2026.106285","url":null,"abstract":"<div><h3>Background</h3><div>Our study aimed to investigate the association of depressive mood and two depressive symptom profiles with the risk of cardiometabolic diseases (CMD) and to explore the underlying mechanisms of these associations through CMD-related metabolites and proteins.</div></div><div><h3>Methods</h3><div>In the Netherlands Epidemiology of Obesity study, depressive mood was measured with the Inventory of Depressive Symptomatology questionnaire, and two depressive symptom profiles, namely atypical energy-related symptom (AES) and melancholic, were created. The AES profile was derived by summing the score of five items: increased sleepiness, increased appetite, weight gain, low energy level and leaden paralysis. The melancholic symptom profile was used as another clinically established symptom profile for comparison with AES. The incidence of CMD (defined as development of cardiovascular diseases or type 2 diabetes (T2D)) was identified during a median follow-up of 6.7 years. Cox proportional hazards models assessed the association between depressive symptom profiles and CMD incidence, adjusted for confounders, while linear regression models examined associations with CMD-related proteins and metabolites identified in the UK Biobank.</div></div><div><h3>Results</h3><div>Compared to participants without depressive mood, those in the severe depressive mood group had the highest risk of developing CMD, with a hazard ratio (HR) of 1.65 (95% CI: 1.22–2.22). Regarding depressive symptom profiles, individuals with a severe AES profile showed a significantly increased risk of T2D (HR: 2.87, 95% CI: 1.92–4.30) compared to those without symptoms, whereas no significant association was observed for the melancholic symptom profile. The AES profile was more strongly associated with CMD-related metabolites, including glycoprotein acetyls, isoleucine and lipoproteins, and proteins predominantly enriched in the cytokine-cytokine receptor interaction pathway.</div></div><div><h3>Conclusion</h3><div>The AES profile is specifically associated with the incidence of T2D, and some specific metabolites and proteins were suggested to influence such association. Acknowledging the heterogeneity of depression may aid in tailoring CMD prevention.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"133 ","pages":"Article 106285"},"PeriodicalIF":7.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973186","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}