{"title":"Social isolation promotes tumor immune evasion via β2-adrenergic receptor","authors":"","doi":"10.1016/j.bbi.2024.10.012","DOIUrl":"10.1016/j.bbi.2024.10.012","url":null,"abstract":"<div><div>Social isolation is a recognized risk factor for tumor initiation and mortality, but the role and mechanisms responsible for social isolation on tumor progression are poorly understood. In this study, we found that social isolation contributed to accelerated tumor growth and induced a remodeling of the tumor immune microenvironment, resulting in immunosuppression. Mechanistically, social isolation triggered the activation of the sympathetic nervous system, leading to impaired CD8<sup>+</sup> T cell antitumor immune responses by activating β-adrenergic receptor 2 (β2-AR), which highly expressed on tumor-infiltrating CD8<sup>+</sup> T cells. Pharmacological inhibition of β2-AR signaling effectively enhanced CD8<sup>+</sup> T cell anti-tumor immune responses and improved the efficacy of anti-PD-1 immunotherapy in the context of social isolation. Thus, our study uncovers a mechanism through which social isolation induces tumor immune evasion and offers potential directions for cancer immunotherapy in socially isolated patients.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442408","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":"CSF and blood signatures support classification of limbic encephalitis subtypes","authors":"","doi":"10.1016/j.bbi.2024.10.018","DOIUrl":"10.1016/j.bbi.2024.10.018","url":null,"abstract":"<div><div>Autoimmune limbic encephalitis (ALE) represents a heterogeneous disease associated with antibodies targeting extracellular (ALE<sub>extra</sub>) epitopes, intracellular (ALE<sub>intra</sub>) epitopes, anti-glutamic acid decarboxylase65 ALE (ALE<sub>GAD65</sub>), and ALE without detectable antibodies (ALE<sub>abneg</sub>). Combining analysis of cellular parameters, investigated by flow cytometry, and soluble parameters in the blood and cerebrospinal fluid (CSF) from a large cohort of 148 ALE patients (33 ALE<sub>extra</sub>, 12 ALE<sub>intra</sub>, 28 ALE-GAD65, 37 ALE<sub>abneg</sub>) in comparison to paradigmatic examples for neuro-inflammatory (51 relapsing remitting MS patients (RRMS)), and neuro-degenerative (34 Alzheimer’s disease patients (AD)) diseases revealed discrete immune signatures in ALE subgroups. Identification of ALE-subtype specific markers facilitated classification of rare ALE-associated tumors, which may prompt further diagnostic efforts in clinical practice. While ALE<sub>intra</sub> exhibited features of neuro-inflammation, ALE<sub>extra</sub> displayed features of neuro-inflammation as well as neuro-degeneration. Moreover, ALE<sub>GAD65</sub> and ALE<sub>abneg</sub> lacked hallmarks of inflammation. This may explain the low efficacy of anti-inflammatory treatment regimens in ALE<sub>GAD65</sub> and presumably also ALE<sub>abneg</sub>.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458321","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":"Extracellular vesicles from L. paracasei improve neuroinflammation, GABA neurotransmission and motor incoordination in hyperammonemic rats","authors":"","doi":"10.1016/j.bbi.2024.10.002","DOIUrl":"10.1016/j.bbi.2024.10.002","url":null,"abstract":"<div><div>Patients with liver cirrhosis may show minimal hepatic encephalopathy (MHE) with motor incoordination and cognitive impairment that reduce life quality and span. Motor incoordination is due to neuroinflammation and enhanced GABAergic neurotransmission in cerebellum. Recent reports support that probiotics, including <em>L. casei</em>, may improve cognitive function in different pathologies and MHE in cirrhotic patients. Extracellular vesicles (EV) are small cell-derived membrane vesicles that carry bioactive molecules released from cells, including bacteria. We hypothesized that EV from <em>Lacticaseibacillus paracasei</em> (LC-EV) could improve neuroinflammation, GABAergic neurotransmission and motor function in MHE. We show that LC-EV treatment reverses glial activation and neuroinflammation in cerebellum and restore motor coordination in hyperammonemic rats. Moreover, ex vivo treatment of cerebellar slices from hyperammonemic rats with LC-EV also reverses glial activation and neuroinflammation, and the enhancement of the TNFR1-S1PR2-BDNF-TrkB and TNFR1-TrkB-pAKT-NFκB-glutaminase-GAT3 pathway<strong>s</strong> and of GABAergic neurotransmission. The results reported support that LC-EV may be used as a therapeutic tool to improve motor incoordination in patients with MHE.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388110","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":"A critical analysis of stress-related gene regulation in isolated and connected individuals","authors":"","doi":"10.1016/j.bbi.2024.09.035","DOIUrl":"10.1016/j.bbi.2024.09.035","url":null,"abstract":"<div><div>This letter responds to the article by Yvonne S. Yang et al. (2024) on the relationship between social isolation, loneliness, and stress-related gene expression, published in Brain, Behavior, and Immunity. The authors’ recruitment methods and use of genome-wide transcriptional profiling to assess the Conserved Transcriptional Response to Adversity (CTRA) are highly commendable, offering a comprehensive understanding of how social isolation impacts immune gene expression. However, we raise concerns about the small sample size, demographic limitations, cross-sectional design, and lack of correction for multiple comparisons, which may affect the study’s generalizability and validity. Despite these limitations, the study provides valuable insights, paving the way for future research to explore the complex interactions between social isolation, loneliness, and health. We recommend that future studies address these limitations to enhance the robustness of findings and the development of effective interventions.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388098","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 treatment with the antipsychotic lurasidone modulates the neuroinflammatory changes associated with the vulnerability to chronic mild stress exposure in female rats","authors":"","doi":"10.1016/j.bbi.2024.10.001","DOIUrl":"10.1016/j.bbi.2024.10.001","url":null,"abstract":"<div><div>Stress exposure is a key risk factor for the development<!--> <!-->of depressive-like conditions. However, despite the higher incidence of Major Depressive Disorder in the female population, classical stress-based experimental paradigms have primarily focused on males. In the present study, we used the well-established chronic mild stress (CMS) paradigm to investigate the development of anhedonia, a cardinal symptom of affective disorders, in the female animals and we also studied the potential effect of the antipsychotic drug lurasidone in normalizing the alterations brought about by stress exposure. We found that three weeks of CMS exposure produced a significant reduction of sucrose intake in 50% of the animals (vulnerable, CMS-V), whereas the others were resilient (CMS-R). The development of an anhedonic phenotype in CMS-V was associated with a significant elevation of different immune markers, such as Complement C3 and C4, and inflammatory cytokines, including INFß and Il1ß in dorsal and ventral hippocampus. Interestingly, sub-chronic treatment with the antipsychotic drug lurasidone was able to revert the anhedonic phenotype while normalizing most of the molecular alterations found in rats vulnerable to CMS exposure. This study extends the ability of lurasidone to normalize the anhedonic phenotype in CMS rats also to females. Moreover, we provide novel evidence on lurasidone’s potential effectiveness in treating mental disorders characterized by immune-inflammatory dysfunction.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388108","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":"A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome","authors":"","doi":"10.1016/j.bbi.2024.10.006","DOIUrl":"10.1016/j.bbi.2024.10.006","url":null,"abstract":"<div><div>Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy that has been studied in several neuroimmune conditions, such as Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and multiple sclerosis. It has also been proposed as a potential treatment option for acute COVID-19 infection and post-acute sequelae of SARS-CoV-2 infection (PASC). IVIG is thought to function by providing the recipient with a pool of antibodies, which can, in turn, modulate immune responses through multiple mechanisms including neutralization of cytokines and autoantibodies, saturation of neonatal fragment crystallizable receptors, inhibition of complement activation, and regulation of T and B cell mediated inflammation. In acute COVID-19, studies have shown that early administration of IVIG and plasmapheresis in severe cases can reduce the need for mechanical ventilation, shorten ICU and hospital stays, and lower mortality. Similarly, in PASC, while research is still in early stages, IVIG has been shown to alleviate persistent symptoms in small patient cohorts. Furthermore, IVIG has shown benefits in another condition which has symptomatic overlap with PASC, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), though studies have yielded mixed results. It is important to note that IVIG can be associated with several potential adverse effects, such as anaphylaxis, headaches, thrombosis, liver enzyme elevations and renal complications. In addition, the high cost of IVIG can be a deterrent for payers and patients. This review provides a comprehensive update on the use of IVIG in multiple neuroimmune conditions, ME/CFS, acute COVID-19, and PASC, as well as covers its history, production, pricing, and mechanisms of action. We also identify key areas of future research, including the need to optimize the use of Ig product dosing, timing, and patient selection across conditions, particularly in the context of COVID-19 and PASC.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399338","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":"Deleterious effects of social isolation on neuroendocrine-immune status, and cancer progression in rats","authors":"","doi":"10.1016/j.bbi.2024.10.005","DOIUrl":"10.1016/j.bbi.2024.10.005","url":null,"abstract":"<div><div>Accumulating evidence indicates that social isolation (SI) in humans and rodents is associated with increased cancer incidence and mortality, yet mediating mechanisms remain elusive. Here, we examine the neuroendocrine and immunological consequences of SI and its short- and long-term physiological impacts in naïve and cancer-bearing rats. Findings indicate that isolated animals experienced a significant decrease in weight compared to controls. Specifically, females showed a marked weight decrease during the first week of isolation. Isolated rats had significantly higher numbers of MADB106 experimental pulmonary metastases. Although mortality rates were higher in isolated tumor-bearing rats, unexpectedly, they exhibited a reduced growth rate of orthotopically implanted MADB106 tumors. Transcriptomic analyses of these excised tumors indicated a major downregulation in the expression of various genes, including those associated with pro-metastatic processes (e.g., EMT). In naïve rats (no cancer), levels of IL-6 increased, and total IgG levels decreased under SI conditions. A mixed effect was found for TNFα, which increased in females and decreased in males. In the central nervous system, isolated rats showed altered gene expression in key brain regions associated with stress responses and social behavior. The paraventricular nucleus of the thalamus emerged as a significantly affected region, along with the bed nucleus of the stria terminalis. Changes were observed in the expression of oxytocin, serotonin, and dopamine receptors. Isolated rats also exhibited greater alterations in hypothalamic–pituitary–adrenal (HPA) axis-related regulation and an increase in plasma CORT levels. Our study highlights the profound impact of SI on metastatic processes. Additionally, the potential detrimental effects of SI on thermoregulation were discussed, emphasizing the importance of social thermoregulation in maintaining physiological stability and highlighting the need to avoid single-caging practices in research. We report neuro-immune interactions and changes in brain gene expression, highlighting the need for further research into these underlying processes to improve outcomes in animal models and potential interventions for cancer patients through increased social support.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388109","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":"Toward a better understanding of T cell dysregulation in autism: An integrative review.","authors":"R J Moreno, R Amara, P Ashwood","doi":"10.1016/j.bbi.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.bbi.2024.10.009","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a highly heterogeneous disorder characterized by impairments in social, communicative, and restrictive behaviors. Over the past 20 years, research has highlighted the role of the immune system in regulating neurodevelopment and behavior. In ASD, immune abnormalities are frequently observed, such as elevations in pro-inflammatory cytokines, alterations in immune cell frequencies, and dysregulated mechanisms of immune suppression. The adaptive immune system - the branch of the immune system conferring cellular immunity - may be involved in the etiology of ASD. Specifically, dysregulated T cell activity, characterized by altered cellular function and increased cytokine release, presence of inflammatory phenotypes and altered cellular signaling, has been consistently observed in several studies across multiple laboratories and geographic regions. Similarly, mechanisms regulating their activation are also disrupted. T cells at homeostasis coordinate the healthy development of the central nervous system (CNS) during early prenatal and postnatal development, and aid in CNS maintenance into adulthood. Thus, T cell dysregulation may play a role in neurodevelopment and the behavioral and cognitive manifestations observed in ASD. Outside of the CNS, aberrant T cell activity may also be responsible for the increased frequency of immune based conditions in the ASD population, such as allergies, gut inflammation and autoimmunity. In this review, we will discuss the current understanding of T cell biology in ASD and speculate on mechanisms behind their dysregulation. This review also evaluates how aberrant T cell biology affects gastrointestinal issues and behavior in the context of ASD.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388112","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":"Analysis of the brain transcriptome, microbiome and metabolome in ketogenic diet and experimental stroke","authors":"","doi":"10.1016/j.bbi.2024.10.004","DOIUrl":"10.1016/j.bbi.2024.10.004","url":null,"abstract":"<div><div>The ketogenic diet (KD) has been shown to be effective in treating various brain pathologies. In this study, we conducted detailed transcriptomic and metabolomic profiling of rat brains after KD and ischemic stroke in order to investigate the effects of KD and its underlying mechanisms. We evaluated the effect of a two-month KD on gene expression in intact brain tissue and after middle cerebral artery occlusion (MCAO). We analyzed the effects of KD on gut microbiome composition and blood metabolic profile as well as investigated the correlation between severity of neurological deficits and KD-induced changes. We found transcriptional reprogramming in the brain after stroke and KD treatment. The KD altered the expression of genes involved in the regulation of glucose and fatty acid metabolism, mitochondrial function, the immune response, Wnt-associated signaling, stem cell development, and neurotransmission, both in intact rats and after MCAO. The KD led to a significant change in the composition of gut microbiome and the levels of amino acids, acylcarnitines, polyunsaturated fatty acids, and oxylipins in the blood. However, the KD slightly worsened the neurological functions after MCAO, so that the therapeutic effect of the diet remained unproven.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388107","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":"Frontiers of Neurodegenerative Disease Treatment: Targeting Immune Cells in Brain Border Regions","authors":"","doi":"10.1016/j.bbi.2024.10.007","DOIUrl":"10.1016/j.bbi.2024.10.007","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDs) demonstrate a complex interaction with the immune system, challenging the traditional view of the brain as an “immune-privileged” organ. Microglia were once considered the sole guardians of the brain’s immune response. However, recent research has revealed the critical role of peripheral immune cells located in key brain regions like the meninges, choroid plexus, and perivascular spaces. These previously overlooked cells are now recognized as contributors to the development and progression of NDs. This newfound understanding opens doors for pioneering therapeutic strategies. By targeting these peripheral immune cells, we may be able to modulate the brain’s immune environment, offering an alternative approach to treat NDs and circumvent the challenges posed by the blood–brain barrier. This comprehensive review will scrutinize the latest findings on the complex interactions between these peripheral immune cells and NDs. It will also critically assess the prospects of targeting these cells as a ground-breaking therapeutic avenue for these debilitating disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388111","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}