Pub Date : 2026-01-08DOI: 10.1016/j.bbih.2026.101172
A. Papageorgiou , D. Chatzistefanidis , M. Nikolakea , N.-R. Karela , M. Gkrampovari , K. Lantavos , D. Bartzi , L. Traikov , S. Markoula
Acute ischemic stroke is one of the leading causes of mortality and morbidity worldwide. The underlying inflammation process following the ischemic event arises as an important factor of great therapeutic interest. Recent research has showcased the roles of B- and T-lymphocytes in the acute post-stroke period, with various types of lymphocytes affecting differently the clinical outcome of the patient. Herein, we reviewed the literature and discussed the functional role of various subpopulations of lymphocytes in recovery and repair of the ischemic tissue as well as their influence on the final outcome of the patient. Additionally, we searched the literature regarding current knowledge on various drugs possibly affecting neuroinflammation or exhibiting a neuroprotective role in the acute post-stroke period.
{"title":"“The emerging role of lymphocytes in post-stroke inflammation: A treatable target and review of current pharmacological evidence in humans\"","authors":"A. Papageorgiou , D. Chatzistefanidis , M. Nikolakea , N.-R. Karela , M. Gkrampovari , K. Lantavos , D. Bartzi , L. Traikov , S. Markoula","doi":"10.1016/j.bbih.2026.101172","DOIUrl":"10.1016/j.bbih.2026.101172","url":null,"abstract":"<div><div>Acute ischemic stroke is one of the leading causes of mortality and morbidity worldwide. The underlying inflammation process following the ischemic event arises as an important factor of great therapeutic interest. Recent research has showcased the roles of B- and T-lymphocytes in the acute post-stroke period, with various types of lymphocytes affecting differently the clinical outcome of the patient. Herein, we reviewed the literature and discussed the functional role of various subpopulations of lymphocytes in recovery and repair of the ischemic tissue as well as their influence on the final outcome of the patient. Additionally, we searched the literature regarding current knowledge on various drugs possibly affecting neuroinflammation or exhibiting a neuroprotective role in the acute post-stroke period.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101172"},"PeriodicalIF":3.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038516","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}
Pub Date : 2026-01-03DOI: 10.1016/j.bbih.2026.101171
Yifan Huang
This review critically synthesizes current neurophysiological findings on the comorbidity between depression and sleep disorders. Drawing upon a multidisciplinary body of literature, the paper delineates overlapping neurochemical, hormonal, and inflammatory mechanisms. Further, it explores the role of astrocytic dysfunction and glutamate-GABA imbalance in reinforcing pathological feedback loops. By adopting an integrative framework, this review underscores the bidirectional and systemic nature of sleep disorder-depression comorbidity, offering insights into shared pathophysiological substrates and potential therapeutic targets for future research.
{"title":"A review of neurophysiological relationships between sleep disorders and depression","authors":"Yifan Huang","doi":"10.1016/j.bbih.2026.101171","DOIUrl":"10.1016/j.bbih.2026.101171","url":null,"abstract":"<div><div>This review critically synthesizes current neurophysiological findings on the comorbidity between depression and sleep disorders. Drawing upon a multidisciplinary body of literature, the paper delineates overlapping neurochemical, hormonal, and inflammatory mechanisms. Further, it explores the role of astrocytic dysfunction and glutamate-GABA imbalance in reinforcing pathological feedback loops. By adopting an integrative framework, this review underscores the bidirectional and systemic nature of sleep disorder-depression comorbidity, offering insights into shared pathophysiological substrates and potential therapeutic targets for future research.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101171"},"PeriodicalIF":3.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980267","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}
Pub Date : 2026-01-02DOI: 10.1016/j.bbih.2026.101170
Emiko O. Kranz , Jemar R. Bather , Xiaoyan Zhang , Virginia W. Chang , Steven W. Cole , Adolfo G. Cuevas
Everyday discrimination is a social determinant of health linked to disease and mortality, with one potential mechanism of this link involving stress-related signaling that “weathers” immune health. Previous research has examined links between discrimination and inflammatory processes derived from innate immune cells, but little is known about the associations of everyday discrimination with lymphoid lineage cells (T cells and B cells) that mediate adaptive immunity. To better understand the potential immunological impact of everyday discrimination, we analyzed the relationship between Everyday Discrimination Scale scores and flow cytometry data from the Health and Retirement Study (n = 6337; mean age = 70 years, SD = 9 years; 58 % female; 71 % White). Primary analyses adjusted for sociodemographic factors and secondary analyses additionally controlled for health behaviors. Weighted results showed that higher levels of discrimination were significantly associated with higher total CD4+ T, CD8+ T, and B cell counts. Follow-up analyses of T and B cell maturity indicated a potential link between higher discrimination levels and mature “terminally differentiated” cells, including CD4+ TEMRA (7.8 % elevation, 95 % CI: 3.8 %–12.0 % elevation, p < 0.001), CD8+ TEMRA (2.9 % elevation, 95 CI: 0.1 %–5.9 % elevation, p = 0.040), and IgD− memory B cells (3.4 % elevation, 95 CI: 0.7 %–6.0 % elevation, p = 0.012), but no significant associations with the immature “naïve” T or B cell subpopulations. Overall, these results suggest that everyday discrimination may contribute to immune aging by promoting the accumulation of terminally differentiated T and B cells, a profile consistent with accelerated immunosenescence in the adaptive immune system.
{"title":"Discrimination exposure and lymphocyte differentiation: Results from the health and retirement study","authors":"Emiko O. Kranz , Jemar R. Bather , Xiaoyan Zhang , Virginia W. Chang , Steven W. Cole , Adolfo G. Cuevas","doi":"10.1016/j.bbih.2026.101170","DOIUrl":"10.1016/j.bbih.2026.101170","url":null,"abstract":"<div><div>Everyday discrimination is a social determinant of health linked to disease and mortality, with one potential mechanism of this link involving stress-related signaling that “weathers” immune health. Previous research has examined links between discrimination and inflammatory processes derived from innate immune cells, but little is known about the associations of everyday discrimination with lymphoid lineage cells (T cells and B cells) that mediate adaptive immunity. To better understand the potential immunological impact of everyday discrimination, we analyzed the relationship between Everyday Discrimination Scale scores and flow cytometry data from the Health and Retirement Study (n = 6337; mean age = 70 years, SD = 9 years; 58 % female; 71 % White). Primary analyses adjusted for sociodemographic factors and secondary analyses additionally controlled for health behaviors. Weighted results showed that higher levels of discrimination were significantly associated with higher total CD4<sup>+</sup> T, CD8<sup>+</sup> T, and B cell counts. Follow-up analyses of T and B cell maturity indicated a potential link between higher discrimination levels and mature “terminally differentiated” cells, including CD4<sup>+</sup> TEMRA (7.8 % elevation, 95 % CI: 3.8 %–12.0 % elevation, <em>p</em> < 0.001), CD8<sup>+</sup> TEMRA (2.9 % elevation, 95 CI: 0.1 %–5.9 % elevation, <em>p</em> = 0.040), and IgD<sup>−</sup> memory B cells (3.4 % elevation, 95 CI: 0.7 %–6.0 % elevation, <em>p</em> = 0.012), but no significant associations with the immature “naïve” T or B cell subpopulations. Overall, these results suggest that everyday discrimination may contribute to immune aging by promoting the accumulation of terminally differentiated T and B cells, a profile consistent with accelerated immunosenescence in the adaptive immune system.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101170"},"PeriodicalIF":3.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980268","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}
Pub Date : 2026-01-02DOI: 10.1016/j.bbih.2026.101168
Cephas B. Appiah , Kishor Kunwar , Rebecca L. Cunningham , J. Thomas Cunningham
Women affected by obstructive sleep apnea (OSA) face an increased risk of cognitive impairment and mood disorders, with emerging evidence suggesting that neuroinflammation plays a significant role in the pathophysiology. OSA causes intermittent hypoxia and activates the immune response in the brain. Additionally, menopause is a separate risk factor that can put women with OSA at an even higher risk of cognitive decline. Although neuroinflammation occurs in OSA, the underlying mechanisms of the neuroinflammatory response are not well understood, and it remains unknown whether ovarian hormones modify these mechanisms. To examine the impact of OSA and hormone status on neuroinflammation, we used a 7-day chronic intermittent hypoxia (CIH) and ovariectomy (OVX) to model OSA and hormone status in female rats, respectively. To examine neuroinflammation, we investigated changes in brain microglia and astrocyte morphology and the number of reactive cells. We used a comprehensive three-dimensional reconstruction and analysis of microglia and astrocytes to study the changes in the morphology of these cells. We focused on brain regions associated with cognitive function (CA1 of the dorsal hippocampus, medial prefrontal cortex – mPFC, caudate and putamen – CP). Specifically, immunofluorescence of Iba1 (microglia marker) and GFAP (astrocyte marker) was conducted, along with measuring indicators of glial reactivity (branching, complexity, cell size, and number of reactive cells). Our results found that there were CIH and hormone effects on neuroinflammation in these brain regions. Microglia activation was impacted by an interaction between CIH and hormone status in all regions examined. In contrast, astrocytes showed no reactivity in all regions examined, regardless of CIH or hormone status. These findings suggest that menopause and OSA may impact microglia remodeling in brain areas associated with cognitive function. Microglia-specific neuroinflammation may be part of early mechanisms that lead to the cognitive impairments observed in CIH and hormone loss in females.
{"title":"Quantitative and morphological analyses reveal microglia-specific neuroinflammation in brain regions linked to cognitive function in ovariectomized and chronic intermittent hypoxia-exposed female rats","authors":"Cephas B. Appiah , Kishor Kunwar , Rebecca L. Cunningham , J. Thomas Cunningham","doi":"10.1016/j.bbih.2026.101168","DOIUrl":"10.1016/j.bbih.2026.101168","url":null,"abstract":"<div><div>Women affected by obstructive sleep apnea (OSA) face an increased risk of cognitive impairment and mood disorders, with emerging evidence suggesting that neuroinflammation plays a significant role in the pathophysiology. OSA causes intermittent hypoxia and activates the immune response in the brain. Additionally, menopause is a separate risk factor that can put women with OSA at an even higher risk of cognitive decline. Although neuroinflammation occurs in OSA, the underlying mechanisms of the neuroinflammatory response are not well understood, and it remains unknown whether ovarian hormones modify these mechanisms. To examine the impact of OSA and hormone status on neuroinflammation, we used a 7-day chronic intermittent hypoxia (CIH) and ovariectomy (OVX) to model OSA and hormone status in female rats, respectively. To examine neuroinflammation, we investigated changes in brain microglia and astrocyte morphology and the number of reactive cells. We used a comprehensive three-dimensional reconstruction and analysis of microglia and astrocytes to study the changes in the morphology of these cells. We focused on brain regions associated with cognitive function (CA1 of the dorsal hippocampus, medial prefrontal cortex – mPFC, caudate and putamen – CP). Specifically, immunofluorescence of Iba1 (microglia marker) and GFAP (astrocyte marker) was conducted, along with measuring indicators of glial reactivity (branching, complexity, cell size, and number of reactive cells). Our results found that there were CIH and hormone effects on neuroinflammation in these brain regions. Microglia activation was impacted by an interaction between CIH and hormone status in all regions examined. In contrast, astrocytes showed no reactivity in all regions examined, regardless of CIH or hormone status. These findings suggest that menopause and OSA may impact microglia remodeling in brain areas associated with cognitive function. Microglia-specific neuroinflammation may be part of early mechanisms that lead to the cognitive impairments observed in CIH and hormone loss in females.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101168"},"PeriodicalIF":3.5,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979616","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}
Pub Date : 2025-12-30DOI: 10.1016/j.bbih.2025.101167
Chun-Ling Dai , Yiting Song , Yonghua Chen , Yunn Chyn Tung , Wei-Chiao Huang , Cheng-Xin Gong , Jonathan F. Lovell
Amyloid beta (Aβ) plaques and hyperphosphorylated tau neurofibrillary tangles (NFTs) are the histopathological hallmarks of Alzheimer's disease (AD) and targets for AD therapeutics. Since Aβ and tau pathologies both drive AD pathogenesis and progression, immunotherapies singularly targeting either Aβ or tau may be limited, and simultaneously targeting multiple epitopes of both Aβ and tau may be an efficacious approach. We developed a novel vaccine including three his-tagged tau peptides, tau1-22, mid-region tau171-191 (taupT181), and tau388-407 (taupS396/S404), as well as two his-tagged Aβ fragments (N-terminal Aβ1-14 and N-terminal pyroglutamate AβpE3-14) with the spontaneous nanoliposome antigen particle (SNAP) system, termed SNAP-AD5. Intramuscular vaccination of nine to ten months old of 3xTg-AD mice and age-matched wild-type control animals with SNAP-AD5 or adjuvant only, once every three weeks for a total of 5 immunizations, simultaneously produced IgG titers of antibody against their specific antigens, significantly decreased Aβ and tau pathologies, and effectively improved cognitive function. SNAP-AD5 was well tolerated without any detectable adverse side effects, including inflammatory responses in the peripheral circulation and in the brain, and hemorrhages in the mouse brain. These results support that SNAP-AD5 simultaneously targeting both Aβ and tau is potentially a promising new approach for treating AD. Further optimization and development of the SNAP-AD5 vaccine for treating AD is warranted.
{"title":"Therapeutic nanoliposome vaccine targeting multiple Aβ and tau epitopes reduces AD-like brain pathologies and rescues cognitive deficits in 3xTg-AD mice","authors":"Chun-Ling Dai , Yiting Song , Yonghua Chen , Yunn Chyn Tung , Wei-Chiao Huang , Cheng-Xin Gong , Jonathan F. Lovell","doi":"10.1016/j.bbih.2025.101167","DOIUrl":"10.1016/j.bbih.2025.101167","url":null,"abstract":"<div><div>Amyloid beta (Aβ) plaques and hyperphosphorylated tau neurofibrillary tangles (NFTs) are the histopathological hallmarks of Alzheimer's disease (AD) and targets for AD therapeutics. Since Aβ and tau pathologies both drive AD pathogenesis and progression, immunotherapies singularly targeting either Aβ or tau may be limited, and simultaneously targeting multiple epitopes of both Aβ and tau may be an efficacious approach. We developed a novel vaccine including three his-tagged tau peptides, tau<sub>1-22</sub>, mid-region tau<sub>171-191</sub> (tau<sub>pT181</sub>), and tau<sub>388-407</sub> (tau<sub>pS396/S404</sub>), as well as two his-tagged Aβ fragments (N-terminal Aβ<sub>1-14</sub> and N-terminal pyroglutamate Aβ<sub>pE3-14</sub>) with the spontaneous nanoliposome antigen particle (SNAP) system, termed SNAP-AD<sub>5</sub>. Intramuscular vaccination of nine to ten months old of 3xTg-AD mice and age-matched wild-type control animals with SNAP-AD<sub>5</sub> or adjuvant only, once every three weeks for a total of 5 immunizations, simultaneously produced IgG titers of antibody against their specific antigens, significantly decreased Aβ and tau pathologies, and effectively improved cognitive function. SNAP-AD<sub>5</sub> was well tolerated without any detectable adverse side effects, including inflammatory responses in the peripheral circulation and in the brain, and hemorrhages in the mouse brain. These results support that SNAP-AD<sub>5</sub> simultaneously targeting both Aβ and tau is potentially a promising new approach for treating AD. Further optimization and development of the SNAP-AD<sub>5</sub> vaccine for treating AD is warranted.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101167"},"PeriodicalIF":3.5,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939125","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}
Pub Date : 2025-12-22DOI: 10.1016/j.bbih.2025.101166
Folkert H. van Bruggen , Roger S. McIntyre
Bipolar disorder (BD) and major depressive disorder (MDD) are highly prevalent, disabling psychiatric illnesses marked by substantial heterogeneity and frequent metabolic and inflammatory comorbidities. Growing evidence implicates low-grade inflammation, immune dysregulation, and insulin resistance (IR) in the pathophysiology, progression, and treatment response of mood disorders. While numerous clinical trials have investigated immunometabolic targeted interventions, outcomes have been inconsistent, due to limited stratification of participants based on underlying biology. This perspective paper aims to identify practical biomarkers and biosignatures to guide patient selection and optimize immunometabolic trial design. We summarize evidence linking neuroinflammation and IR to illness burden, discuss clinical trials targeting these mechanisms, and highlight emerging markers, including extracellular vesicles, monocyte gene expression profiles, and neuron-derived vesicle signatures of IR. No single validated biomarker for identification of immunometabolic phenotype currently exists, but multimodal biosignatures combining genetic, epigenetic, proteomic, and clinical features offer a pragmatic empirical path forward. Integrating these markers with advanced analytic approaches, such as machine learning, holds promise for identifying biologically coherent subgroups most likely to benefit from targeted immunometabolic interventions, accelerating precision medicine for BD and MDD.
{"title":"Neuroinflammation and insulin resistance in major depression and bipolar disorder: Implications for clinical trials evaluating immunometabolic targeted therapies","authors":"Folkert H. van Bruggen , Roger S. McIntyre","doi":"10.1016/j.bbih.2025.101166","DOIUrl":"10.1016/j.bbih.2025.101166","url":null,"abstract":"<div><div>Bipolar disorder (BD) and major depressive disorder (MDD) are highly prevalent, disabling psychiatric illnesses marked by substantial heterogeneity and frequent metabolic and inflammatory comorbidities. Growing evidence implicates low-grade inflammation, immune dysregulation, and insulin resistance (IR) in the pathophysiology, progression, and treatment response of mood disorders. While numerous clinical trials have investigated immunometabolic targeted interventions, outcomes have been inconsistent, due to limited stratification of participants based on underlying biology. This perspective paper aims to identify practical biomarkers and biosignatures to guide patient selection and optimize immunometabolic trial design. We summarize evidence linking neuroinflammation and IR to illness burden, discuss clinical trials targeting these mechanisms, and highlight emerging markers, including extracellular vesicles, monocyte gene expression profiles, and neuron-derived vesicle signatures of IR. No single validated biomarker for identification of immunometabolic phenotype currently exists, but multimodal biosignatures combining genetic, epigenetic, proteomic, and clinical features offer a pragmatic empirical path forward. Integrating these markers with advanced analytic approaches, such as machine learning, holds promise for identifying biologically coherent subgroups most likely to benefit from targeted immunometabolic interventions, accelerating precision medicine for BD and MDD.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101166"},"PeriodicalIF":3.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939123","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}
Pub Date : 2025-12-22DOI: 10.1016/j.bbih.2025.101162
Bengt B. Arnetz , Judith E. Arnetz , Norbert Kaminski , Ryan Tomlin , Pamela Bartlett , Robert Crawford , Andrew Jameson
Background
There is limited description of dynamic changes in stress, inflammation, neuroplasticity, and health literacy during the early phase of HIV infection. This study examined patterns in self-reported stress, neurobiological and neuroplastic markers during the initial 12 months of living with HIV. The study also evaluated possible changes in functional health literacy, that is, patients’ ability to adhere to combination antiretroviral treatment (cART).
Methods
This is an observational cohort study of one female and eleven male and patients with newly diagnosed HIV attending an urban Ryan White funded HIV clinic. Participants responded to a survey and blood was drawn at baseline, and after 1, 3, 6, 9 and 12 months, respectively. The survey measured stress, depression, and health literacy. Blood was analyzed for HIV RNA plasma viral load, CD4 cell count, and biomarkers of stress, inflammation, and neuroplasticity.
Results
Viral load decreased from an initial mean count of 353,714.83 (S.E. 251,243.96) copies/mL to 24.54 (2.01) at 12 months (Wilcoxon Signed Rank Test, p = .012). CD4 cell count increased from 321.08 (48.49) to 541.13 (50.27) cells/mm3 (p = .012). Self-rated stress decreased from 6.83 (.92) to 4.81 (.96), on a 0–10 visual analogue scale (p = .043). Cumulative levels of C-reactive protein (CRP) were inversely associated with cumulative health literacy scores during the 12-month study (Spearman's rho = - 0.634, p = .025).
Conclusion
The study confirms that during the initial 12 months living with HIV, apart from the expected improvement in viral load and CD4, there is a significant decrease in self-perceived stress, but little changes in systems inflammation. The finding of an inverse relationship between levels of a pro-inflammatory marker and health literacy requires further studies.
{"title":"Self-reported health and health literacy, neuroplasticity and neuro-immunological markers during the first 12 months in newly diagnosed people living with HIV: An exploratory study","authors":"Bengt B. Arnetz , Judith E. Arnetz , Norbert Kaminski , Ryan Tomlin , Pamela Bartlett , Robert Crawford , Andrew Jameson","doi":"10.1016/j.bbih.2025.101162","DOIUrl":"10.1016/j.bbih.2025.101162","url":null,"abstract":"<div><h3>Background</h3><div>There is limited description of dynamic changes in stress, inflammation, neuroplasticity, and health literacy during the early phase of HIV infection. This study examined patterns in self-reported stress, neurobiological and neuroplastic markers during the initial 12 months of living with HIV. The study also evaluated possible changes in functional health literacy, that is, patients’ ability to adhere to combination antiretroviral treatment (cART).</div></div><div><h3>Methods</h3><div>This is an observational cohort study of one female and eleven male and patients with newly diagnosed HIV attending an urban Ryan White funded HIV clinic. Participants responded to a survey and blood was drawn at baseline, and after 1, 3, 6, 9 and 12 months, respectively. The survey measured stress, depression, and health literacy. Blood was analyzed for HIV RNA plasma viral load, CD4 cell count, and biomarkers of stress, inflammation, and neuroplasticity.</div></div><div><h3>Results</h3><div>Viral load decreased from an initial mean count of 353,714.83 (S.E. 251,243.96) copies/mL to 24.54 (2.01) at 12 months (Wilcoxon Signed Rank Test, p = .012). CD4 cell count increased from 321.08 (48.49) to 541.13 (50.27) cells/mm<sup>3</sup> (p = .012). Self-rated stress decreased from 6.83 (.92) to 4.81 (.96), on a 0–10 visual analogue scale (p = .043). Cumulative levels of C-reactive protein (CRP) were inversely associated with cumulative health literacy scores during the 12-month study (Spearman's rho = - 0.634, p = .025).</div></div><div><h3>Conclusion</h3><div>The study confirms that during the initial 12 months living with HIV, apart from the expected improvement in viral load and CD4, there is a significant decrease in self-perceived stress, but little changes in systems inflammation. The finding of an inverse relationship between levels of a pro-inflammatory marker and health literacy requires further studies.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101162"},"PeriodicalIF":3.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939124","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}
Pub Date : 2025-12-22DOI: 10.1016/j.bbih.2025.101165
Elise M. Martin, Matthew J. Morales, Niki Y. Li, Maura C. Stoehr, Matthew J. Kern, Madeline F. Winters, Caroline J. Smith
Air pollution and maternal stress during pregnancy are both risk factors for neurodevelopmental disorders and often converge on the same communities. Epidemiological and animal studies suggest that maternal psychosocial stress may worsen the effects of air pollutants on neurodevelopmental outcomes. Previous work utilizing a mouse model of combined prenatal exposure to diesel exhaust particles (DEP) and maternal stress (MS) has found numerous sex-specific effects of DEP/MS exposure on neuroimmune outcomes, dopamine receptors, the gut-brain axis, and social behavior. However, it is unclear how broadly the immune landscape is shifted in the brain and intestinal epithelium following DEP/MS. Here, we analyzed immune gene expression in 5 brain regions important for social behavior and in 3 regions of the intestinal epithelium in both male and female offspring at ∼postnatal day 50, following either DEP/MS or control exposure. We found several interesting overall patterns. First, changes in expression of immune genes such as CD11b and Tlr4 were concentrated in the nucleus accumbens and hippocampus. Tlr4 and Il-17ra mRNA also increased in the jejunum and colon following DEP/MS, but only in females. Second, in the nucleus accumbens, catecholamine-O-methyltransferase (Comt) and dopamine transporter 1 (Slc6a3) gene expression were increased following DEP/MS, indicating increased dopamine degradation at and reuptake from the synapse, respectively. Additionally, dopamine D2 receptor (Drd2) mRNA was decreased following DEP/MS in males. Finally, we observed numerous sex differences in immune gene expression regardless of treatment in both the brain and gut. Together, these findings suggest the nucleus accumbens is a key site for neuroimmune and dopaminergic changes following DEP/MS exposure and indicate female-specific changes in intestinal immunity in young adulthood following these prenatal exposures.
空气污染和怀孕期间的产妇压力都是神经发育障碍的危险因素，而且往往集中在同一社区。流行病学和动物研究表明，母亲的社会心理压力可能会加重空气污染物对神经发育结果的影响。先前的研究利用了一个小鼠模型，将产前暴露于柴油机尾气颗粒（DEP）和母亲压力（MS）相结合，发现了DEP/MS暴露对神经免疫结果、多巴胺受体、肠-脑轴和社会行为的许多性别特异性影响。然而，目前尚不清楚DEP/MS后脑和肠上皮的免疫格局发生了多大程度的变化。在这里，我们分析了DEP/MS或对照暴露后，出生后第50天雄性和雌性后代在5个对社会行为重要的大脑区域和3个肠上皮区域的免疫基因表达。我们发现了几个有趣的总体模式。首先，CD11b、Tlr4等免疫基因的表达变化集中在伏隔核和海马。在DEP/MS后，空肠和结肠的Tlr4和Il-17ra mRNA也增加，但仅在女性中增加。其次，在伏隔核中，DEP/MS后，儿茶酚胺- o -甲基转移酶（Comt）和多巴胺转运蛋白1 （Slc6a3）基因表达增加，分别表明突触的多巴胺降解和从突触的再摄取增加。此外，DEP/MS后，雄性多巴胺D2受体（Drd2） mRNA降低。最后，无论在大脑和肠道中接受何种治疗，我们都观察到免疫基因表达的许多性别差异。总之，这些发现表明伏隔核是DEP/MS暴露后神经免疫和多巴胺能变化的关键部位，并表明这些产前暴露后年轻成年期肠道免疫的女性特异性变化。
{"title":"Effects of combined prenatal exposure to air pollution and maternal stress on immune and dopaminergic gene expression in the gut-brain axis","authors":"Elise M. Martin, Matthew J. Morales, Niki Y. Li, Maura C. Stoehr, Matthew J. Kern, Madeline F. Winters, Caroline J. Smith","doi":"10.1016/j.bbih.2025.101165","DOIUrl":"10.1016/j.bbih.2025.101165","url":null,"abstract":"<div><div>Air pollution and maternal stress during pregnancy are both risk factors for neurodevelopmental disorders and often converge on the same communities. Epidemiological and animal studies suggest that maternal psychosocial stress may worsen the effects of air pollutants on neurodevelopmental outcomes. Previous work utilizing a mouse model of combined prenatal exposure to diesel exhaust particles (DEP) and maternal stress (MS) has found numerous sex-specific effects of DEP/MS exposure on neuroimmune outcomes, dopamine receptors, the gut-brain axis, and social behavior. However, it is unclear how broadly the immune landscape is shifted in the brain and intestinal epithelium following DEP/MS. Here, we analyzed immune gene expression in 5 brain regions important for social behavior and in 3 regions of the intestinal epithelium in both male and female offspring at ∼postnatal day 50, following either DEP/MS or control exposure. We found several interesting overall patterns. First, changes in expression of immune genes such as <em>CD11b</em> and <em>Tlr4</em> were concentrated in the nucleus accumbens and hippocampus. <em>Tlr4</em> and <em>Il-17ra</em> mRNA also increased in the jejunum and colon following DEP/MS, but only in females. Second, in the nucleus accumbens, catecholamine-O-methyltransferase (<em>Comt</em>) and dopamine transporter 1 (<em>Slc6a3</em>) gene expression were increased following DEP/MS, indicating increased dopamine degradation at and reuptake from the synapse, respectively. Additionally, dopamine D2 receptor (<em>Drd2</em>) mRNA was decreased following DEP/MS in males. Finally, we observed numerous sex differences in immune gene expression regardless of treatment in both the brain and gut. Together, these findings suggest the nucleus accumbens is a key site for neuroimmune and dopaminergic changes following DEP/MS exposure and indicate female-specific changes in intestinal immunity in young adulthood following these prenatal exposures.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101165"},"PeriodicalIF":3.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939222","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}
Pub Date : 2025-12-19DOI: 10.1016/j.bbih.2025.101164
Sizhi Wu , Yiwen Lv , Peng Pang , Huachong Xu , Li Deng , Wei Ma , Xiaoyin Chen
Background
Climate factors exert a profound influence on human emotional well-being and physical health. Exposure to a humid heat environment is known to precipitate anxiety-like behaviors and exacerbate the clinical manifestations of influenza; concurrently, mounting evidence has demonstrated a bidirectional regulation between the gut microbiota and human health, suggesting a potential link between environmental stress and microbial homeostasis.
Methods
In this study, C57BL/6J male mice were subjected to a humid heat environment for 3 weeks prior to infection with the influenza A virus. Microbiota composition, metabolites, and intestinal mucosal immunity were comprehensively measured. Furthermore, behavioral phenotypes and neurotransmitter levels were assessed to explore their potential correlations with gut dysbiosis.
Results
Exposure to a humid heat environment aggravated pulmonary and intestinal tissue damage while reshaping the gut microbiota composition and metabolome. This environmental stress precipitated severe pathological injury and robust inflammatory in the intestinal mucosa, characterized by a multifold upregulation of Th1/Th2-related cytokines and the suppressed expression of Ocln, ZO-1, pIgR, and SIgA. Further experiments revealed that the humid heat environment exacerbated neurological deficits in influenza A virus-infected mice, accompanied by a significant reduction in neurotransmitter levels. Conclusions: These data demonstrate that exposure to a humid heat environment exacerbates influenza infection severity through the dysregulation of the intestinal homeostasis and the neuroendocrine system, revealing the potential mechanisms underlying the digestive and nervous system symptoms observed in influenza patients.
{"title":"Distinct actions of the humid heat environment on host gut microbiota, intestinal mucosal immunity, neuroendocrinology in influenza A virus-infected mouse","authors":"Sizhi Wu , Yiwen Lv , Peng Pang , Huachong Xu , Li Deng , Wei Ma , Xiaoyin Chen","doi":"10.1016/j.bbih.2025.101164","DOIUrl":"10.1016/j.bbih.2025.101164","url":null,"abstract":"<div><h3>Background</h3><div>Climate factors exert a profound influence on human emotional well-being and physical health. Exposure to a humid heat environment is known to precipitate anxiety-like behaviors and exacerbate the clinical manifestations of influenza; concurrently, mounting evidence has demonstrated a bidirectional regulation between the gut microbiota and human health, suggesting a potential link between environmental stress and microbial homeostasis.</div></div><div><h3>Methods</h3><div>In this study, C57BL/6J male mice were subjected to a humid heat environment for 3 weeks prior to infection with the influenza A virus. Microbiota composition, metabolites, and intestinal mucosal immunity were comprehensively measured. Furthermore, behavioral phenotypes and neurotransmitter levels were assessed to explore their potential correlations with gut dysbiosis.</div></div><div><h3>Results</h3><div>Exposure to a humid heat environment aggravated pulmonary and intestinal tissue damage while reshaping the gut microbiota composition and metabolome. This environmental stress precipitated severe pathological injury and robust inflammatory in the intestinal mucosa, characterized by a multifold upregulation of Th1/Th2-related cytokines and the suppressed expression of <em>Ocln</em>, <em>ZO-1</em>, <em>pIgR</em>, and <em>SIgA</em>. Further experiments revealed that the humid heat environment exacerbated neurological deficits in influenza A virus-infected mice, accompanied by a significant reduction in neurotransmitter levels. <strong>Conclusions</strong>: These data demonstrate that exposure to a humid heat environment exacerbates influenza infection severity through the dysregulation of the intestinal homeostasis and the neuroendocrine system, revealing the potential mechanisms underlying the digestive and nervous system symptoms observed in influenza patients.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101164"},"PeriodicalIF":3.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939223","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}
Pub Date : 2025-12-18DOI: 10.1016/j.bbih.2025.101163
Faith Dickerson , Emily Katsafanas , Andrea Origoni , Kelly Rowe , Sabahat Khan , Fahad Mukhtar , Shuojja Yang , Victor W. Splan , Robert Yolken
Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with tissue remodeling as well as inflammation and tissue destruction. MMP-9 is of interest since it has been associated with psychiatric disorders including major depressive disorder (MDD). Suicide attempts are a major complication of MDD. However, the association between MMP-9 levels and suicide attempts has not been extensively studied in persons with MDD. Sensitive enzyme immunoassays were employed to measure the levels of MMP-9 in blood samples from 186 persons with MDD receiving hospital care, 92 with a suicide attempt within the previous 30 days and 94 without a recent attempt, as well as 79 persons without a psychiatric disorder. Lifetime suicide attempt history in the MDD group was also recorded. Mixed effects models were employed to compare the MMP-9 levels among the groups adjusted for demographic and clinical variables. Wald tests were used to calculate pairwise comparisons. Employing these models, we found that individuals with MDD and a recent suicide attempt had higher levels of MMP-9 than individuals with MDD without a recent suicide attempt as well as individuals without a psychiatric disorder. There was not a significant difference in MMP-9 levels between the non-psychiatric group and individuals with MDD without a recent suicide attempt, regardless of whether they had a lifetime suicide attempt. Therapeutic modalities to modulate MMP-9 activity are currently being developed. The measurement of MMP-9 might be used to inform future clinical trials of these modalities for the prevention of suicide behaviors in high-risk individuals.
{"title":"Levels of matrix metalloproteinase 9 (MMP-9) are elevated in persons with major depressive disorder who have had a recent suicide attempt","authors":"Faith Dickerson , Emily Katsafanas , Andrea Origoni , Kelly Rowe , Sabahat Khan , Fahad Mukhtar , Shuojja Yang , Victor W. Splan , Robert Yolken","doi":"10.1016/j.bbih.2025.101163","DOIUrl":"10.1016/j.bbih.2025.101163","url":null,"abstract":"<div><div>Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with tissue remodeling as well as inflammation and tissue destruction. MMP-9 is of interest since it has been associated with psychiatric disorders including major depressive disorder (MDD). Suicide attempts are a major complication of MDD. However, the association between MMP-9 levels and suicide attempts has not been extensively studied in persons with MDD. Sensitive enzyme immunoassays were employed to measure the levels of MMP-9 in blood samples from 186 persons with MDD receiving hospital care, 92 with a suicide attempt within the previous 30 days and 94 without a recent attempt, as well as 79 persons without a psychiatric disorder. Lifetime suicide attempt history in the MDD group was also recorded. Mixed effects models were employed to compare the MMP-9 levels among the groups adjusted for demographic and clinical variables. Wald tests were used to calculate pairwise comparisons. Employing these models, we found that individuals with MDD and a recent suicide attempt had higher levels of MMP-9 than individuals with MDD without a recent suicide attempt as well as individuals without a psychiatric disorder. There was not a significant difference in MMP-9 levels between the non-psychiatric group and individuals with MDD without a recent suicide attempt, regardless of whether they had a lifetime suicide attempt. Therapeutic modalities to modulate MMP-9 activity are currently being developed. The measurement of MMP-9 might be used to inform future clinical trials of these modalities for the prevention of suicide behaviors in high-risk individuals.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"51 ","pages":"Article 101163"},"PeriodicalIF":3.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939224","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}
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