Brain, Behavior, and Immunity最新文献

{"title":"From smooth brains to rocky mountains: Quentin Pittman in a Quintessentially Canadian career","authors":"K. Crosby ,&nbsp;A.C. Kentner ,&nbsp;J.B. Kuzmiski ,&nbsp;A. Mouihate ,&nbsp;A. Reid ,&nbsp;S.J. Spencer","doi":"10.1016/j.bbi.2025.02.024","DOIUrl":"10.1016/j.bbi.2025.02.024","url":null,"abstract":"<div><div>This commentary is to honour Dr Quentin Pittman as he steps back from an active role in academia. Pittman’s work leaves a legacy of ground-breaking discoveries, impeccable research, and generous mentorship. His work on thermoregulation, vasopressin, perinatal programming, and hypothalamic function laid a good part of the foundation of the psychoneuroimmunology research we do today. His interest in neuroinflammation led to important findings in animal models of chronic peripheral inflammation including colitis and central inflammatory states observed in epilepsy and multiple sclerosis. His integrative approach, ranging from electrophysiological recordings to whole animal behaviour helped answer physiological questions involving the orchestrated functions and interactions of multiple organs. He is one of a few neuroscientists who raised the question of the contribution of peripheral organs to brain function and plasticity at a time when the field was largely neurocentric. Pittman has enhanced our collective understanding of the effects of neonatal inflammation (and other models of perinatal programming) on the adult brain, and has even revealed key ways in which neurons in the brain communicate with each other, through his work on vasopressin, endocannabinoids, and other transmitters. Altogether, Quentin Pittman’s interdisciplinary work has laid a solid foundation for psychoneuroimmunology research and groundbreaking insight into brain-body integration.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 330-332"},"PeriodicalIF":8.8,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499211","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":"Neuroimmunity at the edge: The skull as a brain – periphery immunological hub in autism spectrum disorder","authors":"Daniel Martins","doi":"10.1016/j.bbi.2025.02.023","DOIUrl":"10.1016/j.bbi.2025.02.023","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 327-329"},"PeriodicalIF":8.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482179","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":"Oleoylethanolamide-producing Lactobacillus paracasei F19 improves metabolic and behavioral disorders by restoring intestinal permeability and microbiota-gut-brain axis in high-fat diet-induced obese male mice","authors":"Luisa Seguella ,&nbsp;Chiara Corpetti ,&nbsp;Jie Lu ,&nbsp;Marcella Pesce ,&nbsp;Silvia Basili Franzin ,&nbsp;Irene Palenca ,&nbsp;Aurora Zilli ,&nbsp;Martina Vincenzi ,&nbsp;Daniele Caprioli ,&nbsp;Andreu Paytuví-Gallart ,&nbsp;Walter Sanseverino ,&nbsp;Sara Rurgo ,&nbsp;Giovanni Sarnelli ,&nbsp;Giuseppe Esposito","doi":"10.1016/j.bbi.2025.02.014","DOIUrl":"10.1016/j.bbi.2025.02.014","url":null,"abstract":"<div><div>Metabolic and mood disorders elicited by chronic exposure of high-fat diet (HFD) are often associated with intestinal dysbiosis and persistent low-grade inflammation in the small intestine. This leads to remodeling of the epithelial barrier with disruption of the neuroepithelial circuits that control energy homeostasis by the gut-brain axis. Therefore, therapies that restoreintestinal microbial niche and barrier function are promising candidates to counter peripheral metabolic challenges that affect behaviors controlled by the brain. The endogenous oleoylethanolamine (OEA) was found to shape the intestinal microbiota profile towards a “lean-like phenotype”, ameliorating pathological profiles of metabolic diseases. Further, OEA displays beneficial effects in several cognitive paradigms and preserves the epithelial barrier integrity, acting as an intestinal “gate-keeper”. Here, we developed an “intestinal OEA factory” for the <em>in-situ</em> and controlled release of OEA by using a probiotic-based delivery system. We engineered the <em>Lactobacillus paracasei F19</em> (LP) to express the human N-acylphosphatidylethanolamine-preferring phospholipase D (NAPE<em>pld</em>) gene and to produce OEA in response to dietary ultra-low oleate supply. We treated 12-week HFD male mice with oleate-probiotic formulations and assessed their impact on metabolic and behavioral dysfunctions, and microbiota-gut-brain signaling after 8 weeks of treatment. NAPE-expressing LP (pNAPE-LP) led to significant reduced weight loss and improved metabolic dysfunction in HFD-treated mice. Further, a parallel improvement in depressive- and anxiety-like phenotypes was associated with the duodenal barrier function retrieval, the restoration of the <em>Firmicutes/Bacteroidetes</em> ratio, and an increase in beneficial bacteria, such as <em>Lactobacillus</em>, <em>Prevotella</em>, and <em>Parabacteroides</em>. The HFD-driven changes both in the enteric and central nervous system were prevented by pNAPE-LP/oleate treatment. Collectively, our data suggest that these effects were mediated by the oleate-dependent release of OEA by pNAPE-LP since no significant effects were observed in HFD mice treated with the native probiotic alone (pLP). This oleate-regulated delivery system of OEA is a safe and efficient probiotic-based strategy for the treatment of metabolic syndrome and related behavioral disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 25-44"},"PeriodicalIF":8.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482197","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":"Mutation S139N on Zika virus prM protein shifts immune response from Asian to contemporary strain","authors":"Jingzhe Shang ,&nbsp;Chao Zhou ,&nbsp;Mengjiao He ,&nbsp;Xing-Yao Huang ,&nbsp;Cheng-feng Qin ,&nbsp;Aiping Wu","doi":"10.1016/j.bbi.2025.02.012","DOIUrl":"10.1016/j.bbi.2025.02.012","url":null,"abstract":"<div><div>Zika virus (ZIKV) has been associated with neurological diseases like microcephaly and Guillain-Barré syndrome. The S139N single mutation on the prM protein of the FSS13025 Asian strain increases the mortality rate in mice. Therefore, it is a valuable tool for studying the impact of immune responses on neural damage. Here, we used single-cell sequencing technology to systematically assess the immune response induced by three ZIKV strains: Asian ancestral strain FSS13025/2010, FSS13025 strain with S139N mutation (FSS13025-S139N), and contemporary strain GZ01/2016. By infecting 1-day-old mice, we observed that the immune spectrum elicited by FSS13025-S139N mutant resembled that induced by the contemporary strain. The FSS13025-S139N strain induces the proliferation of inflammatory microglial cells earlier than the FSS13025 strain, similar to GZ01. A specific cell cluster, Microglia_Ccr7, was induced by the S139N mutant strain and GZ01 strain, which suppresses T cell activation through the PDCD1LG2-PDCD1 signaling pathway. Furthermore, the proliferation of CD8⁺ T cells was weakened and prolonged in S139N strain-infected samples. Finally, we found that the S139N mutant strain causes more apoptosis of neurons compared to the FSS13025 strain. These results indicate that the S139N mutation plays an important role in the immune response pattern of ZIKV and prolongs the duration of neuroinflammation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 247-259"},"PeriodicalIF":8.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464492","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":"Interleukin-6 produces behavioral deficits in pre-pubescent mice independent of neuroinflammation","authors":"Fernando Janczur Velloso,&nbsp;Rebecca Zaritsky,&nbsp;Rouba Y. Houbeika,&nbsp;Nicolas Rios,&nbsp;Steven W. Levison","doi":"10.1016/j.bbi.2025.02.009","DOIUrl":"10.1016/j.bbi.2025.02.009","url":null,"abstract":"<div><div>Maternal inflammation during pregnancy increases the offspring’s risk of developing autism, ADHD, schizophrenia, and depression. Epidemiologic studies have demonstrated that maternal infections stimulate the production of interleukin-6 (IL-6), which can cross the placenta and fetal blood–brain barrier to alter brain development with functional and behavioral consequences. To model the effects of increased IL-6 between weeks 24–30 of human gestation, we injected male and female mice with 75 ng IL-6 twice daily, from P3 to P6. Our published studies have shown that this increases circulating IL-6 two-fold, alters post-pubescent ultrasonic vocalization patterns, reduces sociability, and increases self-grooming.</div><div>However, most neurodevelopmental disorders in humans manifest in children as young as 2 years of age. Hence, a critical unexplored question is whether behavioral changes in immune activation models can be detected in pre-pubescent mice. Therefore, we evaluated early communication, sociability, and repetitive behaviors in pre-pubescent mice following the IL-6 treatment. A second open question is whether the cellular and behavioral changes are secondary to systemic or neuroinflammation. To address this question, we profiled 18 cytokines and chemokines in the circulation and CNS and evaluated eight immune cell types in P7 male and female brains following systemic IL-6 administration. We found an increase in ultrasonic vocalizations with simpler morphologies produced by the IL-6-injected male pups and a decrease in frequency in the female vocalizations upon removal from the nest at P7. The IL-6-treated male pups also socially interacted less when introduced to a novel mouse vs. controls as juveniles and spent almost twice as much time grooming themselves, a phenotype not present in the females. Tactile sensitivity was also increased, but only in the IL-6-treated female mice. The IL-6-treated mice had increased circulating IL-6 and IL-7 and reduced IL-13 at P7 that were no longer elevated at P14. There were no changes in brain levels of IL-6, IL-10, IL-13 or IL-17A mRNAs at P7. Altogether, these studies show that changes in the three core behavioral domains associated with several psychiatric disorders can be detected early in pre-pubescent mice following a transient developmental increase in IL-6. Yet, these behavioral alterations do not require neuroinflammation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 275-288"},"PeriodicalIF":8.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472166","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":"Deficiency of intestinal alkaline phosphatase affects behavior and microglia activity in mice","authors":"Jiajia Dai ,&nbsp;Jinsheng Yang ,&nbsp;Sen Han ,&nbsp;Na Li ,&nbsp;Shiyu Wang ,&nbsp;Suyun Xia ,&nbsp;Hyung-Hwan Kim ,&nbsp;Yonghyun Jun ,&nbsp;Seeun Lee ,&nbsp;Yoshinori Kitagawa ,&nbsp;Fei Xie ,&nbsp;Liuyue Yang ,&nbsp;Shiqian Shen ,&nbsp;Lucy Chen ,&nbsp;Dana P. Turner ,&nbsp;Richard A Hodin ,&nbsp;J.A.Jeevendra Martyn ,&nbsp;Jianren Mao ,&nbsp;Zerong You","doi":"10.1016/j.bbi.2025.02.006","DOIUrl":"10.1016/j.bbi.2025.02.006","url":null,"abstract":"<div><div>The gut microbiota plays crucial roles in the development and functions of the central nervous system (CNS) as well as in modulation of neurobehavior in heath and disease. The gut brush border enzyme intestinal alkaline phosphatase (IAP) is an important positive regulator of gut microbial homeostasis. In mice, IAP is encoded by <em>Akp3</em> gene, which is specifically expressed in the duodenum of the small intestine. IAP deficiency alters gut bacterial composition and gut barrier function. Decreased IAP activity has been observed in aging, gut inflammatory diseases, and metabolic disorders. We hypothesized that this enzyme could also play an important role in modulating neurobehavior. We performed deep sequencing of gut bacterial 16S rRNA and found that IAP deficiency changed gut microbiota composition at various taxonomic levels. Using targeted metabolomic analysis, we also found that IAP deficiency resulted in changes of gut bacteria-derived metabolites in serum and brain metabolism. Neurobehavioral analyses revealed that Akp3^-/- (IAP knockout) mice had decreased basal nociception thresholds, increased anxiety-like behavior, and reduced locomotor activity. Furthermore, Akp3^-/- mice had more pronounced brain microglial phagocytic activity, together with an increase in the activated microglia population. Fecal microbiota transplantation from wildtype to Akp3^-/- mice partially improved neurobehavior and reduced brain microglial phagocytic activity in Akp3^-/- mice. This study demonstrates that deficiency of the endogenous gut-derived host factor IAP induces behavioral phenotype changes (nociception; motor activity, and anxiety) and affects brain microglia activity. Changes in the gut microbiota induced by knocking down <em>Akp3</em> contribute to behavioral changes, which is probably mediated by microglia activity modulated by the gut bacteria-derived metabolites.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 297-310"},"PeriodicalIF":8.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472101","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":"Patient-derived monoclonal LGI1 autoantibodies elicit seizures, behavioral changes and brain MRI abnormalities in rodent models","authors":"Manoj Upadhya ,&nbsp;Alexander Stumpf ,&nbsp;Jack O’Brien-Cairney ,&nbsp;César Cordero Gómez ,&nbsp;Jan Döring ,&nbsp;Julius Hoffmann ,&nbsp;Susanne Mueller ,&nbsp;Yuko Fukata ,&nbsp;Scott van Hoof ,&nbsp;Divya Dhangar ,&nbsp;Max A. Wilson ,&nbsp;Arunvir Atwal ,&nbsp;Richard Rosch ,&nbsp;Gavin Woodhall ,&nbsp;Philipp Boehm-Sturm ,&nbsp;Masaki Fukata ,&nbsp;Jakob Kreye ,&nbsp;Dietmar Schmitz ,&nbsp;Sukhvir K. Wright ,&nbsp;Hans-Christian Kornau ,&nbsp;Harald Prüss","doi":"10.1016/j.bbi.2025.02.019","DOIUrl":"10.1016/j.bbi.2025.02.019","url":null,"abstract":"<div><h3>Objective</h3><div>Limbic encephalitis with leucine-rich glioma inactivated 1 (LGI1) protein autoantibodies is associated with cognitive impairment, psychiatric symptoms, and seizures, including faciobrachial dystonic seizures (FBDS). Patient-derived LGI1-autoantibodies cause isolated symptoms of memory deficits in mice and seizures in rats. Using a multimodal experimental approach, we set out to improve the validity of existing <em>in vivo</em> rodent models to further recapitulate the full clinical syndrome of anti-LGI1 antibody mediated disease.</div></div><div><h3>Methods</h3><div>A monoclonal anti-LGI1 antibody (anti-LGI1 mAb) derived from a patient’s CSF antibody-secreting cell was infused intracerebroventricularly (ICV) into rats and mice for one or two weeks, respectively. Cellular excitability of CA3 pyramidal neurons was determined in hippocampal slices. Structural changes in mouse brains were explored using MRI. Antibody effects on behavior and brain activity of rats were studied using video-EEG.</div></div><div><h3>Results</h3><div>Anti-LGI1 mAbs augmented the excitability of CA3 pyramidal neurons and elicited convulsive and non-convulsive spontaneous epileptic seizures in mice and rats. Mice displayed a hypoactive and anxious phenotype during behavioral testing. MRI revealed acutely increased hippocampal volume after ICV anti-LGI1 mAb infusion. Video-EEG recordings of juvenile rats uncovered two peaks of seizure frequency during the 7-day antibody infusion period resembling the natural progression of seizures in human anti-LGI1 encephalitis.</div></div><div><h3>Interpretation</h3><div>Our data strongly corroborate and extend our understanding of the direct pathogenic and epileptogenic role of human LGI1 autoantibodies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 342-355"},"PeriodicalIF":8.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472171","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":"Distinctive seizure signature in the first video case-control study of a naturally-occurring feline autoimmune encephalitis model","authors":"S.N.M. Binks ,&nbsp;A.H. Crawford ,&nbsp;E. Ives ,&nbsp;L.J. Davison ,&nbsp;A. Fower ,&nbsp;H. Fox ,&nbsp;A. Kaczmarska ,&nbsp;M. Woodhall ,&nbsp;P. Waters ,&nbsp;A.E. Handel ,&nbsp;S.R. Irani ,&nbsp;R. Gutierrez Quintana ,&nbsp;F.A. Chowdhury ,&nbsp;S.H. Eriksson ,&nbsp;A. Pakozdy","doi":"10.1016/j.bbi.2025.02.018","DOIUrl":"10.1016/j.bbi.2025.02.018","url":null,"abstract":"<div><h3>Background and objective</h3><div>Autoimmune encephalitis (AE) is a form of brain inflammation where pathogenic autoantibodies bind surface proteins. In humans, AE is at least as common as infective encephalitis, and seizures are a prominent manifestation. The most common adult human AE is associated with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E). AE in non-human mammals is also recognised, notably the polar bear ‘Knut’, diagnosed with N-methyl D-aspartate receptor antibody encephalitis. LGI1-Ab-E is an emerging cause of spontaneously-arising AE in domestic cats. Our objective was to phenotype the seizure profile of feline LGI1-Ab-E and probe parallels to its human counterpart.</div></div><div><h3>Methods</h3><div>We characterised seizures in naturally-occurring feline LGI1-Ab-E. Three veterinary and two human neurologists independently blind-rated 35 LGI1-antibody positive and negative feline seizure videos from 24 cats (16 LGI1-Ab-E positive, 8 negative). Data analysed included seizure frequency, semiologies and their co-occurrence, localisation, inter-rater agreement, and predictive factors.</div></div><div><h3>Results</h3><div>The mean number of daily seizures at peak was significantly higher in LGI1-antibody positive compared to LGI1-antibody-negative cats (12.6 vs. 1.9/day, pcorr = 0.011). Semiologies statistically significantly enriched in LGI1-Ab-E observations included orofacial automatisms (88/120, 73 % vs. 26/55, 47 %, pcorr = 0.024), salivation (87/120, 73 % vs. 23/55, 42 %, pcorr = 0.004); and mydriasis (79/120, 66 % vs 19/55, 35 %, pcorr = 0.004), and almost exclusively seen in LGI1-Ab-E were circling (39/120, 33 % vs. 1/55, 2 %, pcorr=&lt;0.001) and aggression (14/120, 12 % vs. 0/55, 0 %, non significant after correction). A temporal lobe onset was proposed in 67 % (80/120) of seropositive ratings, compared to 28 % (15/55) LGI1-Ab-E negative (p &lt; 0.0001). Network analysis depicted complex and overlapping relationships between features, akin to the frequent and multifaceted seizures of human LGI1-Ab-E. Orofacial automatisms, mydriasis and temporal lobe localisation were predictive semiological features of feline LGI1-Ab-E.</div></div><div><h3>Significance</h3><div>Feline LGI1-Ab-E represents a clinically distinctive seizure disorder. Our findings highlight the value of studying naturally-occurring, biologically representative animal models which closely mimic human diseases. This bidirectional translational approach confers benefits across species and unites human and veterinary neurology.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 289-296"},"PeriodicalIF":8.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472147","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":"Multi-omics analysis reveals mechanisms of FMT in Enhancing antidepressant effects of SSRIs","authors":"Ying Jiang ,&nbsp;Lingyi Shi ,&nbsp;Yucai Qu ,&nbsp;Mengmeng Ou ,&nbsp;Zhiqiang Du ,&nbsp;Zhenhe Zhou ,&nbsp;Hongliang Zhou ,&nbsp;Haohao Zhu","doi":"10.1016/j.bbi.2025.02.011","DOIUrl":"10.1016/j.bbi.2025.02.011","url":null,"abstract":"<div><h3>Objective</h3><div>This study explores the behavioral and molecular biological impacts of Fecal Microbiota Transplantation (FMT) on depressive mice unresponsive to treatment with Selective Serotonin Reuptake Inhibitors (SSRIs).</div></div><div><h3>Methods</h3><div>Healthy male C57BL/6 mice were used to establish a depression model through chronic restraint stress, treated with fluoxetine, and categorized into Response and Non-response groups. An FMT treatment was added to the Non-response group. Behavioral tests were conducted to assess symptoms of depression. The gut microbiome, plasma metabolites, and hippocampal tissue gene expression and function changes were analyzed using 16S rRNA gene sequencing, LC-MS, and RNA sequencing.</div></div><div><h3>Results</h3><div>FMT significantly improved the depressive symptoms in SSRIs-resistant mice. There was a partial restoration in the diversity and structure of the gut microbiota in the FMT group. Compared to the Non-response group, significant changes were noted in the metabolomic profiles of the FMT group, identifying various differential metabolites. Functional annotations indicated that these metabolites are involved in multiple metabolic pathways. In the Non-response group, certain gene expression levels were significantly restored. GO and KEGG enrichment analyses revealed that these differential genes mainly involve cytokine activity, receptor signaling regulation, and NOD-like receptor signaling pathways. Joint analysis suggested that FMT may exert its effects through an increase in the abundance of g__Paraprevotella, leading to decreased baicalin content and increased Tal2 expression.</div></div><div><h3>Conclusion</h3><div>FMT has potential in improving depressive symptoms unresponsive to SSRIs treatment. Its mechanism may be related to the modulation of the gut microbiota and its metabolites, subsequently affecting gene expression.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 176-188"},"PeriodicalIF":8.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453914","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":"Hippocampal GPR35 is involved in the depression-like behaviors induced by inflammation and mediates the antidepressant effects of fluoxetine in mice","authors":"Xu Kang ,&nbsp;Zhi Xie ,&nbsp;Yan Yang ,&nbsp;Lei Wu ,&nbsp;Heng Xu ,&nbsp;Shuai Zhang ,&nbsp;YuSheng Liang ,&nbsp;Xian Wu","doi":"10.1016/j.bbi.2025.02.010","DOIUrl":"10.1016/j.bbi.2025.02.010","url":null,"abstract":"<div><h3>Background</h3><div>Neuroinflammation plays a pivotal role in the pathogenesis of depression. G protein-coupled receptor 35 (GPR35) is expressed in the brain and plays a role in regulating inflammatory processes. However, its specific role in depression remains unclear. Herein, we investigate the role of GPR35 in depressive behaviors induced by lipopolysaccharide (LPS) in mice.</div></div><div><h3>Methods</h3><div>We employed an LPS-induced depression mouse model and conducted behavioral tests, molecular analyses, and morphological assessments, along with chemogenetic techniques, to investigate the role of GPR35 in depression.</div></div><div><h3>Results</h3><div>Our results showed a significant increase in GPR35 expression in the brain of LPS-treated mice. Both pharmacological inhibition and genetic knockdown of GPR35 alleviated LPS-induced depressive-like behaviors by mitigating neuroinflammation, oxidative stress, synaptic plasticity deficits, and TLR4/NF-κB signaling in mice. Conversely, pharmacological activation of GPR35 notably exacerbated LPS-induced depressive-like behaviors in mice. Additionally, the GPR35 antagonist ML-145 effectively prevented LPS-induced inflammation responses in BV-2 microglia cells. Moreover, fluoxetine treatment effectively mitigated the upregulation of hippocampal GPR35 expression induced by LPS in mice. However, administration of the GPR35 agonist zaprinast reversed the antidepressant effects of fluoxetine. Chemogenetic activation of hippocampal glutamatergic neurons attenuated LPS-induced depression-like behaviors, accompanied by decreased GPR35 expression.</div></div><div><h3>Conclusion</h3><div>Hippocampal GPR35 is closely associated with depressive behaviors in the inflammatory model, highlighting its potential as a therapeutic target for antidepressant drug development.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 189-213"},"PeriodicalIF":8.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464582","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}