Neuroimmunomodulation最新文献

{"title":"The saNeuroGut Initiative: Investigating the Gut Microbiome and Symptoms of Anxiety, Depression, and Posttraumatic Stress.","authors":"Michaela A O'Hare, Patricia C Swart, Stefanie Malan-Müller, Leigh L van den Heuvel, Erine Bröcker, Soraya Seedat, Sian M J Hemmings","doi":"10.1159/000542696","DOIUrl":"10.1159/000542696","url":null,"abstract":"<p><strong>Introduction: </strong>Common mental disorders, such as anxiety disorders, depression, and posttraumatic stress disorder (PTSD), present a substantial health and economic burden. The gut microbiome has been associated with these psychiatric disorders via the microbiome-gut-brain axis. However, previous studies have focused on the associations between the gut microbiome and common mental disorders in European, North American, and Asian populations. As part of the saNeuroGut Initiative, we assessed associations between gut microbial composition and self-reported symptoms of anxiety, depression, and posttraumatic stress (PTS) among South African adults.</p><p><strong>Methods: </strong>Participants completed validated, online self-report questionnaires to evaluate symptoms of state anxiety, trait anxiety, depression, and PTSD. Eighty-six stool-derived microbial DNA samples underwent sequencing of the V4 region of the 16S rRNA gene to characterise gut bacterial taxa in the sample.</p><p><strong>Results: </strong>No significant associations were observed between symptom severity scores and alpha (Shannon and Simpson indices) and beta (Aitchison distances) diversity metrics. Linear regression models revealed that the abundances of Catenibacterium, Collinsella, and Holdemanella were significantly positively associated with the severity of PTS symptoms.</p><p><strong>Conclusion: </strong>Catenibacterium, Collinsella, and Holdemanella have each previously been associated with various psychiatric disorders, with Catenibacterium having been positively associated with symptoms of PTSD in another South African cohort. This study sheds light on the relationship between the human gut microbiome and symptoms of anxiety, depression, and PTS in a South African adult sample.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"1-15"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676256","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":"Gestational Hypothyroxinemia Shifts Th1/Th17 Immunity and Innate Lymphoid Cell Balance in the Adult Offspring during the Presymptomatic Stage of Experimental Autoimmune Encephalomyelitis.","authors":"Sebastian Gatica, Nicolas Paillal, Ma Andreina Rangel-Ramírez, Luis Méndez, Alonso Fernández-Tello, Alexis M Kalergis, Susan M Bueno, Pablo A González, Jorge A Soto, Felipe Simon, Leandro J Carreño, Felipe Melo-Gonzalez, Claudia A Riedel","doi":"10.1159/000545578","DOIUrl":"10.1159/000545578","url":null,"abstract":"<p><strong>Introduction: </strong>Thyroid hormone homeostasis during pregnancy is crucial for proper neurodevelopment and cognitive capacity during adulthood. Accumulating evidence reveals that gestational hypothyroxinemia (HTX) modulates the immune response of the adult offspring.</p><p><strong>Methods: </strong>In the present study, adult mice gestated in HTX and their euthyroid counterparts were induced with a mild form of experimental autoimmune encephalomyelitis (EAE), a widespread model of multiple sclerosis, and analyzed at baseline and 7 days after EAE induction.</p><p><strong>Results: </strong>Levels of circulating IL-17 were significantly lower in mice gestated in HTX at both timepoints, while circulating IFN-γ was significantly higher only in mice gestated in HTX, 7 days after EAE induction. A significant increase in type 1 innate lymphoid cells (ILC1) was found only in mice gestated in HTX 7 days after EAE induction, while type 3 innate lymphoid cells (ILC3) populations showed no variation. Interestingly, a significant increase of Th17 CD4+ cells was found only in mice of euthyroid gestation, 7 days after EAE induction.</p><p><strong>Conclusion: </strong>These results highlight the repercussions of thyroid hormone impairment in utero at adult ages while dissecting on the pathogenesis of EAE in terms of Th1/Th17 balance from an innate immune perspective. These findings contribute to the advancement of our comprehension of the presymptomatic stage of EAE, unveiling new paths for basic and translational research in the field of neuroinflammation.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"126-138"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002694","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 Metabolomic Mind: Microbial Metabolite Programming of Microglia.","authors":"Branden G Verosky, Michael T Bailey, Tamar L Gur","doi":"10.1159/000545484","DOIUrl":"10.1159/000545484","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota is increasingly recognized as a critical regulator of brain function, influencing neurodevelopment, brain physiology, and disease vulnerability in part through its interactions with microglia, the resident immune cells of the central nervous system. Microbial metabolites, beginning prenatally and persisting throughout the lifespan, modulate fundamental aspects of microglial biology.</p><p><strong>Summary: </strong>Microglia from germ-free mice exhibit persistent immaturity, altered energy metabolism, and blunted inflammatory responses, which can be partially reversed by microbial colonization or supplementation with specific bacterial metabolites. Short-chain fatty acids, tryptophan-derived indoles, and secondary bile acids have emerged as key microbial mediators that regulate microglial development, metabolism, and immune function, whereas certain inflammatory metabolites, such as trimethylamine <sc>n</sc>-oxide, disrupt microglial homeostasis, and worsen neurodegeneration.</p><p><strong>Key messages: </strong>These findings reveal distinct metabolite-driven pathways linking microbial composition to microglial phenotypes, positioning the microbiome as a potential key influencer of neurodevelopmental trajectories and the pathophysiology of psychiatric and neurological disorders. Despite recent advances, major knowledge gaps persist in understanding the precise molecular intermediaries and mechanisms through which metabolite signaling to microglia shapes susceptibility or resilience to brain-based disorders. Understanding both the bacterial metabolomic landscape and its collective impact on microglial programming holds substantial therapeutic promise, offering avenues to target microbial metabolite production or administer them directly to modulate disease susceptibility.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"139-149"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780652","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 Immune Cell Subsets in the Development of Postoperative Cognitive Dysfunction in Surgical Patients under Anesthesia.","authors":"Chao Ying, Feng Lin","doi":"10.1159/000548491","DOIUrl":"10.1159/000548491","url":null,"abstract":"<p><strong>Background: </strong>Postoperative cognitive dysfunction (POCD) affects 10-54% of surgical patients, especially the elderly. It is increasingly recognized as a major perioperative complication driven by neuroinflammatory mechanisms. While physiological postoperative inflammation supports wound healing and recovery, pathological hyperactivation of immune pathways leads to blood-brain barrier disruption, immune cell infiltration, and long-term cognitive impairment.</p><p><strong>Summary: </strong>This review examines the contribution of innate and adaptive immune cell subsets to POCD pathogenesis. Activated microglia, infiltrating monocytes, and neutrophils initiate neuroinflammatory cascades through cytokine release, while dysregulated T-cell balance (increased Th17 cells, reduced regulatory T cells) exacerbates dysfunction. Key molecular pathways involve damage-associated molecular patterns, complement activation, and impaired neurotrophin signaling. Clinical biomarkers such as IL-6, TNF-α, and S100B show predictive value, with sensitivity of 65-85% and specificity of 75-90%. Current therapeutic strategies include dexmedetomidine, anti-inflammatory agents, and comprehensive perioperative optimization.</p><p><strong>Key messages: </strong>POCD is a frequent postoperative complication linked to immune dysregulation and neuroinflammation. Both innate and adaptive immune cells play central roles, with microglial polarization and T-cell imbalance as major drivers. Biomarkers such as IL-6, TNF-α, and S100B can support risk stratification and early intervention. Immunomodulatory therapies and perioperative optimization represent promising approaches to reduce POCD incidence and improve patient outcomes.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"306-321"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207092","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":"Plasma IL-6 Levels as a Biomarker for Behavioral Changes in Alzheimer's Disease.","authors":"Fumihiko Yasuno, Atsushi Watanabe, Yasuyuki Kimura, Yumeka Yamauchi, Aya Ogata, Hiroshi Ikenuma, Junichiro Abe, Hiroyuki Minami, Takashi Nihashi, Kastunori Yokoi, Nobuyoshi Shimoda, Kensaku Kasuga, Takeshi Ikeuchi, Akinori Takeda, Takashi Sakurai, Kengo Ito, Takashi Kato","doi":"10.1159/000547726","DOIUrl":"10.1159/000547726","url":null,"abstract":"<p><strong>Introduction: </strong>Behavioral and psychological symptoms of dementia (BPSD) significantly affect the quality of life for patients with Alzheimer's disease (AD) and contribute to caregiver burden. Although systemic inflammation is implicated in AD pathophysiology, the specific role of peripheral immune activity - particularly interleukin-6 (IL-6) - in relation to BPSD remains unclear, especially regarding its independent effects from central neuroinflammation.</p><p><strong>Methods: </strong>We conducted a cross-sectional study of 23 biomarker-confirmed patients diagnosed with AD or prodromal AD. Plasma and cerebrospinal fluid (CSF) levels of IL-6, IL-1β, tumor necrosis factor-α, and C-reactive protein were measured. BPSD was assessed using the Dementia Behavior Disturbance (DBD) scale. Central neuroinflammation was quantified via 11C-DPA-713 translocator protein positron emission tomography (TSPO-PET). Stepwise multiple linear regression and Bayesian analyses were used to identify predictors of BPSD severity.</p><p><strong>Results: </strong>Plasma IL-6 emerged as the only significant predictor of DBD scores in frequentist and Bayesian regression models. Other demographic, cognitive, and inflammatory variables, including CSF IL-6 and TSPO-PET binding, showed no significant association with behavioral symptoms. No correlation was observed between plasma and CSF IL-6 levels, nor between plasma IL-6 and TSPO-PET measures.</p><p><strong>Conclusion: </strong>Peripheral IL-6 is significantly associated with BPSD severity in AD, independently of central inflammatory markers. This finding suggests a distinct peripheral immune mechanism underlying neuropsychiatric symptoms, potentially mediated via systemic pathways such as vagus nerve signaling or gut-brain-immune interactions. Peripheral IL-6 may serve as a clinically relevant biomarker and therapeutic target for behavioral disturbances in AD.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"233-244"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874219","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":"Expression of Concern.","authors":"","doi":"10.1159/000548698","DOIUrl":"10.1159/000548698","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"32 1","pages":"334"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708724","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":"Immunological Approaches in the Diagnosis and Treatment of Psychiatric Disorders: A Historical Overview.","authors":"Norbert Müller","doi":"10.1159/000542784","DOIUrl":"10.1159/000542784","url":null,"abstract":"<p><strong>Background: </strong>For over 130 years, scientists have been suggesting that infection and inflammation may play a role in psychosis and other psychiatric disorders. First attempts to treat psychosis by immune-modulating therapies were made early in the last century; however, after the development of antipsychotics in the 1950s, scientific interest shifted away from immunological aspects of psychiatric disorders to the involvement of catecholamines, in particular dopamine, in psychosis.</p><p><strong>Summary: </strong>Antipsychotic treatment was not as successful as expected, so the 1990s saw renewed interest in inflammation and psychoneuroimmunological research in schizophrenia and beyond. In parallel, advances in immunological research methods allowed immunological and inflammatory mechanisms to be studied in more detail.</p><p><strong>Key messages: </strong>Clinical studies and meta-analyses have demonstrated positive effects of anti-inflammatory treatment in certain patients with psychiatric disorders. More research is needed to elucidate exactly how immunological mechanisms result in disease pathophysiology, with the aim to improve anti-inflammatory and personalized treatments.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"16-23"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731063","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":"Regular Positive Human Contacts Do Not Improve Pigs' Response to a Lipopolysaccharide Immune Challenge.","authors":"Oceane Schmitt, Christian Knecht, Birgit Sobczak, Hana Volkmann, Ulrike Gimsa, Jean-Loup Rault","doi":"10.1159/000544748","DOIUrl":"10.1159/000544748","url":null,"abstract":"<p><strong>Introduction: </strong>Little is known about the effects of a positive human-animal relationship on animal health and resilience. This study investigated the effects of regular positive human-animal interactions on pigs' response to an immune challenge.</p><p><strong>Methods: </strong>Twenty-four female pigs were recruited at weaning (5 weeks old), and siblings of similar weights were allocated to either the positive contact treatment with positive contacts given by a human to groups of 3 pigs in their home pen or the control treatment only exposed to a human standing immobile and silently in front and outside their home pen. Treatment sessions were applied over 9 consecutive weeks, lasted 10 min per group, and occurred twice daily (morning and afternoon), 3 days a week. At 16 weeks of age, pigs were submitted to an immune challenge, which consisted of a single intravenous administration of lipopolysaccharide (LPS; 2 µg/kg). The sickness behaviours of pigs were observed using scan sampling every 5 min over 6 h post-administration, recording somnolence, vomiting, diarrhoea, cramping, shivering, and panting. Blood samples were taken before the LPS administration, after 1 h and 3 h. Blood plasma was analysed to quantify tumour necrosis factor alpha, interleukins 6 and 10, immunoglobulin A, and cortisol concentrations, and blood serum was analysed to quantify a brain-derived neurotrophic factor. Behavioural and physiological data were statistically analysed using general linear models in R.</p><p><strong>Results: </strong>Both treatments showed signs of sickness behaviour following LPS administration, but the two treatments did not differ in the frequency, severity of sickness behaviours, or length of recovery or in the blood plasma concentration of cytokines and cortisol measured.</p><p><strong>Conclusion: </strong>Therefore, regular exposure to positive contacts with a human over several weeks, although leading to the development of a positive human-animal relationship, did not enhance the pigs' response to this immune challenge or the immune parameters measured in this study.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"83-93"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537454","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":"Exosomes and microRNA: A New Form of Remote and Bidirectional Neuroimmunomodulation?","authors":"Rainer H Straub","doi":"10.1159/000547243","DOIUrl":"10.1159/000547243","url":null,"abstract":"<p><p><p>Background: There exists the well-known crosstalk between brain and immune system, which has much to do with energy regulation in the body. The selfish brain dominates energy distribution in the presence of threats like predators, wounding with hemorrhage, food scarcity, thirst, cold, and heat. The selfish immune system dominates energy allocation during infection and wounding with infection. Often, the two major organ systems selfishly inhibit each other to govern energy self-supply. However, sometimes they can help each other in early situation with threats (immediate mutual assistance). The brain influences the immune system by means of hard-wired nerve fibers and their neurotransmitters and through hormones from brain-controlled endocrine glands. The immune system influences structures of the brain through soluble factors like cytokines, migrating immune cells, and surface receptors (e.g., of cytokines) on sensory nerve fibers. After the appearance of microRNA, this classical view of neuroimmunomodulation needs some revision. Summary: This view of neuroimmunomodulation has recently been expanded by experimental work in stress research [Semin Immunol. 2014;26(5):394-401 and Trends Immunol. 2017;38(10):768-76]. Next to classical connectors of brain and immune system, exosome microRNA may play an outstanding role in this bidirectional crosstalk. This review systematically analyzes sources of microRNA in the brain and effects of this microRNA on target immune function. Vice versa, microRNAs of distinct immune cells are demonstrated how they might interfere with various brain functions. Key Messages: This review has the character of a theory that should stimulate new research in order to define - in a single publication - the origin of microRNA in the brain and its influence on the target in immune cells and vice versa. The field of neuroimmunomodulation should include these new microRNA pathways to obtain a full picture of bidirectional interactions between the two selfish organ systems. </p>.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"161-212"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584281","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":"Damage on Central Nervous System Cells Elicited by Innate Immune Activation: Lessons to be Learnt from the Intracellular Bacterium <i>Brucella abortus</i>.","authors":"Ana María Rodríguez, Julia Rodríguez, Alex D Guano, Guillermo H Giambartolomei","doi":"10.1159/000548181","DOIUrl":"10.1159/000548181","url":null,"abstract":"<p><strong>Background: </strong>The central nervous system (CNS) relies primarily on innate immunity for protection. While these immune responses help to fight pathogens, they can also cause irreversible damage because of the CNSs limited regenerative capacity. Therefore, it is crucial to understand which CNS cells contribute to pathogen clearance but in doing so potentially damage surrounding tissue.</p><p><strong>Summary: </strong>Neurobrucellosis, caused by intracellular bacteria from the genus Brucella, is an inflammatory disease. Recent studies have shown that astrocytes and microglia are the source of this neuroinflammation. In response to Brucella infection, they create a microenvironment in the CNS which leads to the destabilization of the glial structure, the damage of the blood-brain barrier and neuronal demise. Using Brucella as an example, this review of CNS glial cells responses to an intracellular bacterium shows how inflammation generates damage on tissue instead of infection resolution.</p><p><strong>Key messages: </strong>Since the network of pathophysiological interactions described here are not necessarily limited to brucellosis, it is reasonable to assume that these mechanisms could be relevant in other neurological disorders in which inflammation plays a key role.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"245-257"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033909","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}