Brain Behavior and Immunity Integrative最新文献

{"title":"Same signals, different conductors: A gut–brain perspective on bone regulation—parallels and particularities","authors":"Lu Qiao ,&nbsp;Wei-Ting Zeng ,&nbsp;Yu-Xin Zhu ,&nbsp;Man-Sau Wong ,&nbsp;Hui-Hui Xiao","doi":"10.1016/j.bbii.2026.100151","DOIUrl":"10.1016/j.bbii.2026.100151","url":null,"abstract":"<div><div>Osteoporosis, a systemic metabolic bone disorder characterized by reduced bone mineral density (BMD) and compromised bone microarchitecture, poses a significant public health challenge globally. Emerging evidence underscores the pivotal role of the gut-brain-bone axis in modulating skeletal homeostasis through a complex interplay of neurotransmitters, immune responses, and endocrine signals. This review elucidates the molecular mechanisms by which gut-derived and brain-derived signals converge, diverge, or synergize to regulate bone metabolism. We explore the contrasting effects of sympathetic and parasympathetic nervous systems on bone remodeling, highlighting the role of neurotransmitters such as serotonin, dopamine, and GABA. Furthermore, we discuss the contribution of gut microbiota to bone health via the synthesis of neurotransmitters and modulation of immune responses. The endocrine interactions between the brain and gut, involving hormones like cortisol, leptin, and GLP-1, are also examined. By identifying potential drug targets, this review aims to pave the way for novel, mechanism-based interventions for osteoporosis, emphasizing the importance of a holistic approach that integrates gut, brain, and bone health.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Itrīfal Mulayyin, a promising drug to manage Shaqīqa Muzmin (chronic migraine): A comprehensive review","authors":"Iram Jahan,&nbsp;Abdul Rafeh Wani,&nbsp;Mohd Asif Hussain Usmani,&nbsp;Usamah Ahmad","doi":"10.1016/j.bbii.2026.100150","DOIUrl":"10.1016/j.bbii.2026.100150","url":null,"abstract":"<div><h3>Background</h3><div>Migraine is a highly disabling neurological disorder and the second leading cause of disability-adjusted life years (DALYs) among neurological conditions worldwide. Chronic migraine (<em>Shaqīqa Muzmin</em>) is associated with inadequate management of acute episodes, medication overuse, psychological stress, obesity, and systemic inflammation. Increasing evidence implicates the gut–brain axis—a bidirectional communication network involving neural, immune, and endocrine pathways—in migraine pathophysiology. Alterations in gut microbiota, pro-inflammatory cytokines, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, and neurotransmitters such as serotonin, dopamine, and calcitonin gene-related peptide (CGRP) are considered central to this mechanism.</div></div><div><h3>Objective</h3><div>This review explores the therapeutic potential of <em>Itrīfal Mulayyin</em>, a classical Unani polyherbal formulation, in chronic migraine through its effects on the gut–brain axis, humoral balance, and neuroinflammatory pathways.</div></div><div><h3>Methods</h3><div>Data were synthesized from classical Unani texts, the Unani Formulary of India, and modern biomedical literature. Pharmacological activities of the formulation’s constituents were examined in relation to migraine and gut–brain regulation.</div></div><div><h3>Results</h3><div><em>Itrīfal Mulayyin</em> is a semisolid formulation comprising <em>Terminalia chebula</em>, <em>Terminalia bellirica</em>, <em>Phyllanthus emblica</em>, <em>Rheum emodi</em>, <em>Convolvulus scammonia</em>, <em>Operculina turpethum</em>, <em>Foeniculum vulgare</em>, <em>Lavandula stoechas</em>, <em>Pistacia lentiscus</em>, and sugar base (<em>Qiwām</em>). Classical literature attributes to it three core actions: (i) <em>Munaqqi Dimāgh</em> (brain cleanser) – detoxifying humoral imbalance; (ii) <em>Mulayyin-i-Am‘a</em> (laxative) – enhancing gastrointestinal motility and waste elimination; and (iii) <em>Musakkin-i-Alam</em> (analgesic) – alleviating pain. Modern pharmacology supports these actions, demonstrating antioxidant, anti-inflammatory, neuroprotective, and gut-modulating properties of its ingredients. Together, these mechanisms suggest a regulatory role on the gut–brain axis and a potential in reducing migraine frequency and severity.</div></div><div><h3>Conclusion</h3><div>By bridging Unani theory and biomedical evidence, <em>Itrīfal Mulayyin</em> emerges as a promising complementary therapy for chronic migraine. Its multimodal actions warrant systematic pharmacological validation and clinical trials to establish its efficacy and safety in migraine management.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100150"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysbiosis and the modern lifestyle: Mechanisms, health impacts, and microbiome based interventions","authors":"Swapnanil Mahanta,&nbsp;Keya Nath,&nbsp;Kristipriya Boruah,&nbsp;Tapash Chakraborty","doi":"10.1016/j.bbii.2025.100146","DOIUrl":"10.1016/j.bbii.2025.100146","url":null,"abstract":"<div><div>The human gut microbiota, comprising more than 100 trillion microorganisms, is at the heart of digestive, metabolic, immune, and neuroendocrine health. But with advancing lifestyle, factors such as diets rich in processed food, physical inactivity, chronic stress, circadian disturbance, overuse of medications, and exposure to environmental toxins are progressively linked to microbial dysbiosis, a perturbation that underlies a wide range of diseases. This review critically discusses the pathways by which novel exposures interfere with gut microbial balance, emphasizing roles of hormonal changes, deranged motility, nutrient malabsorption, and biofilm disruption. We discuss how dysbiosis induces gastrointestinal diseases like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), metabolic and endocrine illness like obesity and polycystic ovary syndrome (PCOS), neuropsychiatric disorders, autoimmune disease, and even respiratory and skin disease through gut-organ axes. In addition, the review offers evidence-based approaches to restore microbial homeostasis through high-fiber and polyphenol-dense diets, physical activity, stress reduction, wise use of medications, and innovative microbiome-directed therapies such as probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Directions for the future including microbiome profiling, designer probiotics, and AI-directed personalized interventions are addressed. This review highlights the importance of bringing microbiota-focused strategies into public health policy and lifestyle medicine to reduce the global burden of disorders related to dysbiosis.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100146"},"PeriodicalIF":0.0,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced immune fitness is associated with poorer physical and mental health of Turkish community pharmacy visitors","authors":"Lucia Mosquera Macia ,&nbsp;Emina Išerić ,&nbsp;Nurgül Nefçi ,&nbsp;Gökçe Çölkesenoğlu ,&nbsp;Serel Ulusoy ,&nbsp;Nilay Aksoy ,&nbsp;Joris C. Verster","doi":"10.1016/j.bbii.2025.100144","DOIUrl":"10.1016/j.bbii.2025.100144","url":null,"abstract":"<div><div>Adequate immune fitness, i.e. the body’s capacity to respond to health challenges (such as infections) by activating an appropriate immune response is vital to maintain health and prevent or resolve disease. Aim of the current survey among n = 450 Turkish pharmacy visitors was to investigate the sociodemographic, health, and lifestyle factors that are related to experiencing reduced immune fitness. The analyses revealed that individuals with reduced immune fitness reported significantly poorer general health and immune fitness, significantly poorer sleep, and significantly poorer mood, and a significantly lower quality of life. The analyses revealed significantly poorer immune fitness among individuals with a chronic disease, and those with a lower education level. A regression analysis evaluated possible predictors of reduced immune fitness. The strongest predictor of reduced immune fitness was having a chronic disease. Other significant contributing factors were older age, lower BMI, poorer sleep quality, greater anxiety, greater fatigue, lower hostility, and attaining a less healthy daily diet. In conclusion, reduced immune fitness is associated with having chronic diseases, and poorer physical and mental health.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145739337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic evaluation of herbal drug Paeonia officinalis in the management of generalized anxiety disorder – A single blind randomized placebo controlled trial","authors":"Swaleha Akhtar ,&nbsp;Tanzeel Ahmad ,&nbsp;Jamal Azmat ,&nbsp;S Javed Ali","doi":"10.1016/j.bbii.2025.100145","DOIUrl":"10.1016/j.bbii.2025.100145","url":null,"abstract":"<div><h3>Background</h3><div>Generalized Anxiety Disorder (GAD) is a prevalent psychiatric condition characterized by persistent and excessive worry, often accompanied by physical symptoms such as restlessness, fatigue, and difficulty concentrating. Conventional treatments, including benzodiazepines and selective serotonin reuptake inhibitors (SSRIs), have limitations such as side effects and dependence potential. Unani medicine offers herbal alternatives with promising therapeutic potential. <em>Ood saleeb (Paeonia officinalis)</em> has been historically used for neurological and psychological disorders, but its efficacy in GAD remains underexplored.</div></div><div><h3>Methods</h3><div>A single blind randomized placebo-controlled trial was conducted involving participants diagnosed with GAD based on DSM-5 criteria. Patients were divided into two groups: one receiving <em>Ood saleeb</em> and the other receiving a placebo treatment. Grading of anxiety was done using the Hamilton Anxiety Rating Scale (HAM-A) at baseline, 15th, 30th,45th, and 60th day. Secondary outcomes included Restlessness, Insomnia, Palpitations, Fatigue and Irritability. Data were analyzed using appropriate statistical methods to determine efficacy.</div></div><div><h3>Results</h3><div><em>Ood saleeb</em> significantly reduced HAM-A scores compared to placebo, demonstrating notable anxiolytic effects. Improvements in subjective parameters were observed in the treatment group. No severe adverse effects were reported, suggesting a good safety profile. The findings indicate that Ood saleeb may offer a natural alternative for managing GAD with minimal side effects.</div></div><div><h3>Conclusion</h3><div><em>Ood saleeb (Paeonia officinalis)</em> exhibited significant anxiolytic properties in patients with GAD, supporting its potential as a complementary or alternative treatment in Unani medicine. Further large-scale studies are recommended to validate these findings.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"13 ","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New mechanisms of aging: From vascular to neurological system","authors":"Qingwen Hu ,&nbsp;Fuyuan Zhang ,&nbsp;Hanxuan Wang ,&nbsp;Ruixiang Wang ,&nbsp;Dan Zhang ,&nbsp;Rong Fu ,&nbsp;Menglin Zhu ,&nbsp;Hao Zhang ,&nbsp;Meng Gu ,&nbsp;Chunhong Shao ,&nbsp;Yi Zhun Zhu","doi":"10.1016/j.bbii.2025.100143","DOIUrl":"10.1016/j.bbii.2025.100143","url":null,"abstract":"<div><div>Aging is marked by progressive physiological decline, with vascular aging emerging as a pivotal contributor to chronic diseases, including cardiovascular disorders and neurological disorders. As emphasized by Thomas Sydenham’s axiom, “a man is as old as his arteries,” age-dependent arterial remodeling—characterized by endothelial dysfunction, oxidative stress, and arterial stiffening—compromises cerebral perfusion and blood-brain barrier integrity. These vascular alterations disrupt cerebral homeostasis, fostering hypoperfusion, microvascular damage, and neurotoxic inflammation, which synergize with amyloid-β and tau pathologies to accelerate cognitive decline. Understanding the processes of arterial aging is crucial, as numerous age-related cardiovascular and cerebrovascular diseases stem from alterations in arterial function or are exacerbated by functional and phenotypic changes in the arteries. Prioritizing vascular health in aging populations may thus offer a dual benefit: delaying arterial aging and preserving cognitive function, addressing one of the most urgent public health challenges of the 21st century. This review highlights the critical role of vascular aging in the pathophysiology of neurological disorders and discusses emerging therapeutic targets for their alleviation.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100143"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and proteomic evidence supporting the significance of individualized homeopathic treatment in depression","authors":"Ubiratan Cardinalli Adler,&nbsp;Lia Lira Olivier Sanders","doi":"10.1016/j.bbii.2025.100141","DOIUrl":"10.1016/j.bbii.2025.100141","url":null,"abstract":"<div><div>This Letter to the Editor addresses concerns raised about our recently published N-of-1 trial on an individualized integrative approach for major depressive disorder. N-of-1 designs inherently control for baseline variability, as each participant serves as their own control across randomized treatment periods. The psychiatric diagnosis was confirmed by experienced clinicians using DSM-5 criteria, consistent with pragmatic practice. Although the participant entered the double-blind phase in remission, within-subject analyses showed a clinically meaningful 78 % improvement on the Beck Depression Inventory-II with homeopathic <em>Sulphur</em> compared with placebo, corroborated by parallel SF-12 Mental Component findings. Proteomic analyses further revealed immune-inflammatory modulation, offering biological convergence. These clinical and molecular findings support the validity of this individualized integrative approach and call for replication in more N-of-1 trials.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100141"},"PeriodicalIF":0.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sn-2 palmitate attenuates neuroinflammation in aged mice via sex-specific modulation of the microbiota-gut-brain axis","authors":"Lin Zhu ,&nbsp;En Thong Low ,&nbsp;Hong Zhang ,&nbsp;Zhenbo Xu ,&nbsp;Peijin Tong ,&nbsp;Jianchun Wan ,&nbsp;Boyan Gao ,&nbsp;Liangli (Lucy) Yu ,&nbsp;Yaqiong Zhang","doi":"10.1016/j.bbii.2025.100140","DOIUrl":"10.1016/j.bbii.2025.100140","url":null,"abstract":"<div><div>Previous studies have demonstrated that sn-2 palmitate promotes neurodevelopment in early-life hosts (e.g., infants and newly weaned mice). However, its neuroprotective effects in aged mice and the underlying mechanisms remain unclear. In this study, we employed 18-month-old C57BL/6 mice as an aging model. After six months of dietary supplementation with sn-2 palmitate at varying concentrations (47.62 %, 59.15 % or 75.79 %), both male and female aged mice exhibited attenuated neuroinflammation accompanied by the reduced expression of glial activation markers (IBA-1 and GFAP). Notably, this neuroprotective effect was mediated by regulating the microbiota-gut-brain axis in a sex-dependent manner and was most pronounced in aged mice supplemented with 75.79 % sn-2 palmitate. In females, it enriched gut microbiota belonging to the genera <em>Lachnoclostridium, Dubosiella,</em> and <em>Muribaculum,</em> up-regulated phenylalanine, tyrosine and tryptophan biosynthesis, and phenylalanine metabolism pathways in serum and enhanced fecal sphingolipid excretion, collectively reducing systemic inflammation. Meanwhile, the up-regulation of arginine and proline metabolism in the hippocampus enhanced its energy buffering capacity and stress resilience. In males, sn-2 palmitate increased the abundances of <em>Akkermansia, Parabacteroides,</em> and <em>Blautia</em> genera, which enhanced tryptophan metabolism and elevated its serum derivatives, while reducing circulating glycerolipid levels and promoting their fecal excretion. The tryptophan-glycerolipid metabolic regulation exerted a dual anti-inflammatory effect, suppressing systemic inflammation and directly attenuating neuroinflammation. Together, our findings provide novel insights into the neuroprotective potential of dietary sn-2 palmitate in aged models and establish a foundation for developing precision dietary interventions tailored to sex differences, with potential implications for improving brain health in aging populations.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systemic and dialectical paradigm for Psychoneuroendocrineimmunology and integrated care science","authors":"Francesco Bottaccioli ,&nbsp;Anna Giulia Bottaccioli","doi":"10.1016/j.bbii.2025.100138","DOIUrl":"10.1016/j.bbii.2025.100138","url":null,"abstract":"<div><div>The integrated care needs of a philosophical paradigm. Psychoneuroendocrineimmunology can be it, provided that a consensus is created on its profound meaning. What is Psychoneuroendocrineimmunology (PNEI)? It is not Neuroendocrinoimmunology. PNEI (also called PNI, Psychoneuroimmunology) describes the relationships of mutual influence between the psyche and biological systems and between the whole organism and the physical and social environment, showing the scientific inconsistency of the reductionist dogma that makes the psyche a mere epiphenomenon of brain activity. We are in a phase of research that allows the definitive overcoming of the dualistic conception of the human being without falling into the trap of the mind-brain identity, in the reduction of the psychic dimension to the biological one, from which it undoubtedly originates but on which it influences. To this end, it is essential to critique the philosophical foundations of contemporary reductionism, while, at the same time, highlighting the theoretical-conceptual paradigm that underlies PNEI research and the practice of treatments that integrate medicine and psychology, which descend from this paradigm.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extra virgin olive oil supplementation attenuates hippocampal inflammation in high-fat diet-induced obesity animals with a depressive phenotype","authors":"Ariadni Mesquita Peres ,&nbsp;Ricardo Maia Dantas ,&nbsp;Aline Candida Ferreira ,&nbsp;Ana Caroline Silva Silveira ,&nbsp;Letícia Cunha Pereira de Souza ,&nbsp;Giovana Barbosa Raphaelli ,&nbsp;Diorlon Nunes Machado ,&nbsp;Lucas dos Santos da Silva ,&nbsp;Jéssica Hauschild Taday ,&nbsp;Danusa Mar Arcego ,&nbsp;João Paulo Maires Hoppe ,&nbsp;Randriely Merscher Sobreira de Lima ,&nbsp;Patricia P. Silveira ,&nbsp;Carlos Alexandre Netto ,&nbsp;José Cláudio Fonseca Moreira ,&nbsp;Marina Concli Leite ,&nbsp;Daniel Pens Gelain ,&nbsp;Carla Dalmaz ,&nbsp;Rachel Krolow S.S. Bast","doi":"10.1016/j.bbii.2025.100137","DOIUrl":"10.1016/j.bbii.2025.100137","url":null,"abstract":"<div><div>Obesity and depression are major public health concerns that often co-occur. High-fat diets (HFD) in rodents are commonly used to model both conditions, triggering hippocampal inflammation. In this context, extra virgin olive oil (EVOO) supplementation, with its anti-obesogenic, anti-inflammatory, antioxidant and neuroprotective properties, shows potential as a therapeutic intervention. This study investigates the effects of EVOO supplementation in adult male and female rats receiving HFD. Depressive-like behavior was assessed through the Porsolt forced swim and splash tests, while neuroinflammation, activation of glial cells, and neuroplasticity-related proteins, were evaluated in the hippocampus. Our results showed that HFD induced depressive-like-behavior, which EVOO supplementation significantly alleviated by reducing immobility time and anhedonia. EVOO supplementation also reduced IL-1β, IL-6 and TNF-α levels and increased the immunocontent of neuroplasticity-related proteins in the hippocampus of female rats. In males with obesity, EVOO supplementation decreased glial fibrillary acidic protein (GFAP) and IL-6 levels in the hippocampus. Additionally, EVOO decreased the immunoreactivity of Toll-like receptor-4 (TLR-4) and ionized calcium-binding adaptor molecule-1 (IBA-1) in the hippocampus of both sexes. The clustering analysis made using the behavioral and neurochemical parameters measured in these animals further highlight the effectiveness of EVOO in attenuating HFD effects on these markers, with females displaying greater heterogeneity forming four distinct clusters and males exhibiting a clearer separation between groups. These findings suggest EVOO supplementation as a promising non-pharmacological strategy to counteract factors associated with obesity and depression, particularly by modulation of hippocampal neuroinflammation, astrocytic reactivity, and neuroplasticity.</div></div>","PeriodicalId":100197,"journal":{"name":"Brain Behavior and Immunity Integrative","volume":"12 ","pages":"Article 100137"},"PeriodicalIF":0.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}