Neuroimmunomodulation最新文献

{"title":"KETO-MOOD: Ketogenic Diet for Microbiome Optimization and Overcoming Depression - A Protocol for a Randomized Controlled Trial.","authors":"Katarzyna Hongler, Astrid Lounici, Erin Maurer, Ueli Lanz, Orsolya Szathmari, Yvonne Reuter, Sandra Nussbaum, Ines Steinborn, Annika Haedrich, Melina A Mölling, Ulf Wein, Iona Bocek, Luca Hersberger, Annette B Brühl, Undine E Lang, Timur Liwinski","doi":"10.1159/000542979","DOIUrl":"10.1159/000542979","url":null,"abstract":"<p><strong>Introduction: </strong>Major depressive disorder (MDD) significantly impacts millions worldwide, with limited success in achieving remission for many patients, leading to high disease burden and increased suicide risk. Psychotherapy and antidepressants, although effective, do not provide relief for all, prompting the search for alternative treatments. Ketogenic diets have demonstrated positive effects on brain health. Our study aims to investigate the efficacy of the ketogenic diet in alleviating MDD symptoms, filling a critical gap in psychiatric treatment options and offering a novel dietary approach with potential to mitigate disease burden and enhance mental well-being.</p><p><strong>Methods: </strong>This phase 2 randomized controlled trial will evaluate the efficacy of a 10-week program of dietitian counseling and ketogenic meal provision versus an intervention with similar dietetic contact promoting a healthy, insulin-lowering, non-ketogenic diet. The primary outcome is the change in the Patient Health Questionnaire nine-item depression score. Secondary outcomes include cognitive and affective mindfulness, self-efficacy, sleep, cognitive function, work and social adjustment, and various immunological, metabolic, and microbiome markers at weeks 6 and 10.</p><p><strong>Conclusion: </strong>This study addresses a critical gap in depression treatment by exploring the ketogenic diet's potential as a metabolic mood enhancing intervention. Given the global impact of depression and limitations of current therapies, this research is valuable for exploring previously underappreciated neuroprotective and metabolic mechanisms and clinical benefits.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"36-48"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Analysis between Serum NLRP1 Inflammasome and Depression in Acute Stage of Stroke.","authors":"Song Li, Kun Geng, Lin Yang, Yaling Zhang, Xiaoyang Tao, Jierui Cai, Linyang Li, Zemin Luo, Birendra Mahato, Yonglei Liu, Xiaoling Yin, Hiu Cai, Jishuai Zhao, Heyan Chen, Lixia Wang","doi":"10.1159/000546439","DOIUrl":"10.1159/000546439","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to investigate the correlation between serum NLRP1 inflammasome level and depressive state in acute stage of stroke.</p><p><strong>Methods: </strong>A total of 102 patients with acute stroke who were hospitalized for the first time in the Department of Neurology of the First Affiliated Hospital of Dali University from April 2023 to October 2023 were included, and 80 of them met the inclusion criteria. On the 7th day of admission, the patients were evaluated using the 24-item Hamilton Depression Scale (HAMD-24) and were divided into 31 patients in the acute stage of stroke depression group and 49 patients in the acute stage of stroke non-depression group. The general clinical data of patients were collected, the unified Stroke Scale score (NIHSS) and Pittsburgh Sleep Quality Index score (PSQI) were performed, and fasting serum was collected at 8 a.m. the next morning. NLRP1 inflammatory bodies (NLRP1, ASC, Caspase1) and inflammatory factors IL-1β, IL-18, IL-10, tumor necrosis factor (TNF)-α were detected.</p><p><strong>Results: </strong>(1) The incidence of depression in acute stage of stroke was 38.75%. (2) There were statistically significant differences in PSQI and NIHSS scores between the two groups (p < 0.05), and the scores were correlated with the degree of depression, and were positively correlated with HAMD-24 scores (p < 0.05). (3) The expression levels of NLRP1, IL-18, and TNF-α in serum were significantly different between the two groups (p < 0.01), and the expression levels were correlated with the degree of depression, and were positively correlated with HAMD-24 scores (p < 0.05). There were no significant differences in the expression levels of serum IL-1β, IL-10, Caspase-1 and ASC (p > 0.05). (4) Further analysis by stepwise fitting binary logistic regression showed that NIHSS score, NLRP1, and IL-18 level were independent risk factors for depression in acute stage of stroke (p < 0.05). (5) NIIHSS score, NLRP1, and IL-18 receiver operating characteristic curve area have certain predictive value for the occurrence and development of acute depression during stroke.</p><p><strong>Conclusion: </strong>The more severe the neurological impairment and sleep disorder, the higher the expression level of NLRP1 inflammasome in blood, and the more severe the depression in acute stage of stroke.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"150-160"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melanocortin Receptor-Mediated Anti-Inflammatory Effect of Acthar® Gel in Human Myeloid Cells.","authors":"Kyle Hayes, Dale Wright","doi":"10.1159/000547302","DOIUrl":"10.1159/000547302","url":null,"abstract":"<p><p><p>Introduction: Acthar® Gel, a complex mixture of porcine adrenocorticotropic hormone analogs that activates all 5 melanocortin receptor (MCR) subtypes, is an approved noncorticosteroid treatment for multiple sclerosis (MS) exacerbations.</p><p><strong>Methods: </strong>MCR expression and anti-inflammatory effects of Acthar Gel in human monocyte-derived macrophages (MDMs) and human brain-derived microglia were investigated following lipopolysaccharide stimulation in vitro.</p><p><strong>Results: </strong>MC1R was expressed at substantially higher levels than the other MCR subtypes in human MDMs and was the only MCR gene detected in human adult microglia. As shown by microarray gene expression analysis, polarization of MDMs to a pro-inflammatory phenotype increased the expression and secretion of interleukin-6, tumor necrosis factor α, and CXC motif chemokine ligand 10, which were inhibited in a dose-dependent manner with Acthar Gel treatment.</p><p><strong>Conclusions: </strong>These results are consistent with previous insights that Acthar Gel has an immunomodulatory mechanism distinct from glucocorticoids alone and suggest that Acthar Gel can improve clinical outcomes in MS and other inflammation-mediated central nervous system disorders by inhibiting multiple pro-inflammatory cytokine signaling pathways. </p>.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"213-219"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution Has neither Goals nor Aims, Only Needs.","authors":"Hugo Besedovsky, Adriana Del Rey","doi":"10.1159/000549378","DOIUrl":"10.1159/000549378","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"335-336"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12685323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"16th German Endocrine-Brain-Immune Network (GEBIN) Conference 2025 with the European Psychoneuroimmunology Network (EPN) and the Working Group Neuroimmunology of the German Society for Immunology (AKNI) Satellite Symposia, September 2-6, 2025, Giessen, Germany: Abstracts.","authors":"","doi":"10.1159/000547756","DOIUrl":"10.1159/000547756","url":null,"abstract":"<p><p>There is no abstract GEBIN 2025 Conference.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"32 Suppl 1","pages":"1-31"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the Nervous-Endocrine System and Immune Response, in Human Chagas Disease Pathology.","authors":"Florencia Belén González, Brenda Dinatale, Wilson Savino, Oscar Adelmo Bottasso, Ana Rosa Pérez","doi":"10.1159/000548813","DOIUrl":"10.1159/000548813","url":null,"abstract":"<p><p><p>Background: Chronic Chagas disease can affect multiple organs, most notably the heart and gastrointestinal tract, and in some cases, the nervous system. However, the underlying pathophysiological mechanisms of this parasitic infection remain incompletely understood. Summary: Evidence from studies in both mice with acute Trypanosoma cruzi (T. cruzi) infection and in patients with Chagas disease has revealed a range of immune-neuroendocrine alterations and metabolic disruptions. In this review, we highlight key findings in human Chagas disease related to these abnormalities and discuss their potential contributions to disease pathogenesis. Key Messages: In the context of chronic Chagas disease, the neuroendocrine-immune axis operates as a dynamic interface, integrating systemic immune-endocrine processes with localized responses in the central nervous system (CNS), with each component influencing disease advancement and organ-specific pathology through distinct yet interconnected mechanisms. </p>.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"322-333"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12659659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Gut-Brain Axis in Modulating the Impact of Sterile Inflammation on Neuroimmune Responses in Neurodegenerative Diseases: Alzheimer's Disease and Parkinson's Disease.","authors":"Pei-Zhi Ling, Ka-Hing Wong, Yuen-Shan Ho, Wai-Yin Cheng, Raymond Chuen-Chung Chang","doi":"10.1159/000547746","DOIUrl":"10.1159/000547746","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence has demonstrated the important role of gut microbiota in host physiology, affecting host immunity. The gut-brain axis has been identified between the central nervous system and the gut microbiota, indicating bidirectional communication between the two systems.</p><p><strong>Summary: </strong>Microbial imbalance (in other words, gut dysbiosis) can lead to chronic systemic inflammation, resulting in neuroinflammation as an example of sterile inflammation. Three major pathways in causing neuroinflammation from chronic systemic inflammation by the gut microbiota via the gut-brain axis are discussed throughout the article. This includes the inflammasome signaling, altered permeability of the blood-brain barrier by the short-chain fatty acids, and oxidative stress.</p><p><strong>Key messages: </strong>Through understanding that gut dysbiosis is capable of modulating neuroinflammation, the use of probiotics in neurodegenerative diseases can be investigated to assess their therapeutic potential. Increasing clinical studies show positive results on the use of probiotics in neurodegenerative diseases, yet further evidence is required to validate their clinical effectiveness.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"220-232"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Oral Administration of the Probiotic Lactobacillus rhamnosus GG on the Proteomic Profiles of Cerebrospinal Fluid and Immunoregulatory Signaling in the Hippocampus of Adult Male Rats.","authors":"Kelsey M Loupy, Lamya'a M Dawud, Cristian A Zambrano, Thomas Lee, Jared D Heinze, Ahmed I Elsayed, James E Hassell, Heather M D'Angelo, Matthew G Frank, Steven F Maier, Lisa A Brenner, Christopher A Lowry","doi":"10.1159/000544842","DOIUrl":"10.1159/000544842","url":null,"abstract":"<p><strong>Introduction: </strong>The microbiome-gut-brain axis, by modulating bidirectional immune, metabolic, and neural signaling pathways in the host, has emerged as a target for the prevention and treatment of psychiatric and neurological disorders. Oral administration of the probiotic bacterium Lactobacillus rhamnosus GG (LGG; ATCC 53103) exhibits anti-inflammatory effects, although the precise mechanisms by which LGG benefits host physiology and behavior are not known. The goal of this study was to explore the general effects of LGG on the cerebrospinal fluid (CSF) proteome and a biological signature of anti-inflammatory signaling in the central nervous system (CNS) of undisturbed, adult male rats.</p><p><strong>Methods: </strong>Liquid chromatography-tandem mass spectrometry-based proteomics were conducted using CSF samples collected after 21 days of oral treatment with live LGG (3.34 × 107 colony-forming units (CFU)/mL in the drinking water (resulting in an estimated delivery of ∼1.17 × 109 CFU/day/rat) or water vehicle. Gene enrichment analysis (using DAVID, v. 6.8) and protein-protein interactions (using STRING, v. 11) were used to explore physiological network changes in CSF. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was performed to assess gene expression changes of anti-inflammatory cytokines in the hippocampus. Genes associated with anti-inflammatory signaling that were analyzed included Il10, Tgfb1, Il4, and IL-4-responsive genes, Cd200, Cd200r1, and Mrc1 (Cd206).</p><p><strong>Results: </strong>Oral LGG administration altered the abundance of CSF proteins, increasing the abundance of five proteins (cochlin, NPTXR, reelin, Sez6l, and VPS13C) and decreasing the abundance of two proteins (CPQ, IGFBP-7) in the CSF. Simultaneously, LGG increased the expression of Il10 mRNA, encoding the anti-inflammatory cytokine interleukin 10, in the hippocampus.</p><p><strong>Conclusion: </strong>Oral LGG altered the abundance of CSF proteins associated with extracellular scaffolding, synaptic plasticity, and glutamatergic signaling. These data are consistent with the hypothesis that oral administration of LGG improves memory and cognition, and promotes a physiological resilience to neurodegenerative disease, by increasing glutamatergic signaling and promoting an anti-inflammatory environment in the brain.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"94-109"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Sex-Specific Effects of Early Life Adversity and Chronic Psychosocial Stress during Adulthood on Bone Are Mitigated by Mycobacterium vaccae NCTC 11659 in Mice.","authors":"Dorothea Gebauer, Tamara Schimmele, Giulia Mazzari, Benjamin T Krüger, Msgana Zemui, Anita Ignatius, Dominik Langgartner, Melanie Haffner-Luntzer, Stefan O Reber","doi":"10.1159/000543507","DOIUrl":"10.1159/000543507","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic stress is a major burden in our society and increases the risk for various somatic and mental diseases, in part via promoting chronic low-grade inflammation. Interestingly, the vulnerability for chronic stress during adulthood varies widely among individuals, with some being more resilient than others. For instance, women, relative to men, are at higher risk for developing typical stress-related diseases, including depression and post-traumatic stress disorder (PTSD). Moreover, the experience of early life adversity (ELA) may increase an individuals' vulnerability for chronic stress during adulthood (CAS), possibly due to its association with chronic inflammation. Because severe consequences of stress-induced immune activation are a dysregulated endochondral ossification, delayed long-bone growth, and bone regeneration following fracture, the aim of this study was to investigate the sex-specific effects of ELA alone or in combination with CAS on bone. As enhancement of an individuals' immunoregulatory potential by repeated administrations of a heat-inactivated preparation of Mycobacterium vaccae NCTC (National Collection of Type Cultures) 11659 has been shown to promote stress resilience in mice, we further aimed to investigate if M. vaccae NCTC 11659 also protects against the negative effects of ELA/CAS on bone.</p><p><strong>Methods: </strong>Male and female C57BL/6N mice were subjected to ELA using a maternal separation (MS) model. CAS was induced by either using the chronic subordinate colony housing (CSC) paradigm in males or the social instability paradigm (SIP) in females. The effects on bone were evaluated by µCT, histological, and gene expression analysis. M. vaccae NCTC 11659 was administered repeatedly s.c. prior to CAS.</p><p><strong>Results: </strong>No cumulative impact of ELA and CAS on bone could be detected. Female mice seem to be more susceptible to ELA while male mice to CAS. Importantly, repeated M. vaccae NCTC 11659 administrations were able to mitigate the negative consequences of stress on bone in both sexes.</p><p><strong>Conclusion: </strong>Our results support the hypotheses that the negative effects of ELA and CAS on bone are highly sex-dependent. Moreover, repeated s.c. administrations with immunoregulatory microorganisms might be a future therapeutic option for stress-related bone disorders.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"49-66"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Perinatal Microbiota-Gut-Brain Axis: Implications for Postpartum Depression.","authors":"Marie Armbruster, Paul Forsythe","doi":"10.1159/000543691","DOIUrl":"10.1159/000543691","url":null,"abstract":"<p><strong>Background: </strong>Pregnancy and childbirth are accompanied by widespread maternal physiological adaptations and hormonal shifts that have been suggested to result in a period of vulnerability for the development of mood disorders such as postpartum depression (PPD). There is also evidence of peripartum changes in the composition of the gut microbiota, but the potential contribution of intestinal microbes to the adaptations, or subsequent vulnerabilities, during this period are unknown.</p><p><strong>Summary: </strong>Here, we outline key pathways involved in peripartum adaptations including GABAergic signaling, oxytocin, and immunomodulation that are also associated with susceptibility to mood disorders and present evidence that these pathways are modulated by gut microbes. We also discuss the therapeutic potential of the microbiota-gut-brain axis in PPD and identify future directions for research to help realize this potential.</p><p><strong>Key messages: </strong>Peripartum adaptations are associated with shifts in gut microbial composition. Disruption of GABAergic, oxytocin, and immunomodulatory pathways may contribute to vulnerability of mood disorders including PPD. These key adaptive pathways are modulated by intestinal microbes suggesting a role for the gut microbiota in determining susceptibility to PPD. More research is needed to confirm relationship between gut microbes and PPD and to gain the mechanistic understanding required to realize the therapeutic potential of microbiota-gut-brain axis in this mood disorder.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"67-82"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}