Igor Rafael Correia Rocha, Maggie R Finch, Jayson B Ball, Michael E Harland, Madison Clements, Suzanne Green-Fulgham, Guiyun Song, Yi Liu, Daniel Banov, Linda R Watkins
{"title":"An initial investigation of transcutaneous delivery of plasmid DNA encoding interleukin-10 for the treatment of psoriatic skin conditions.","authors":"Igor Rafael Correia Rocha, Maggie R Finch, Jayson B Ball, Michael E Harland, Madison Clements, Suzanne Green-Fulgham, Guiyun Song, Yi Liu, Daniel Banov, Linda R Watkins","doi":"10.1016/j.bbi.2024.10.031","DOIUrl":"10.1016/j.bbi.2024.10.031","url":null,"abstract":"<p><p>Psoriasis is a chronic immune-mediated skin disorder characterized by intense local inflammation, epidermal hyperplasia, and leukocyte infiltration. Current treatment approaches for psoriasis aim to alleviate symptoms and prevent disease progression, including systemically administered drugs with whole body side effects. Despite some advances in psoriasis treatment, success has been quite limited. To begin to address this challenge, we undertook an initial investigation of whether transcutaneous delivery of an endogenous anti-inflammatory cytokine could provide an effective, local treatment of psoriatic-like skin conditions. To do this, we utilized a previously documented rodent model of psoriasis, induced via a single topical application of Imiquimod (IMQ) to the shaved back of rats. The therapeutic approach used for this initial investigation was delivery of plasmid DNA encoding rat interleukin-10 (pDNA-rIL10), a non-viral gene therapy approach previously shown to be effective in suppressing neuroinflammatory disorders after localized delivery either intracerebrally or intrathecally. Translation of this CNS therapeutic for use in psoriatic-like skin disorders required reformulation to enable transcutaneous delivery. Toward that end, pDNA-rIL10 was topically applied in Lipoderm HMW, a base explicitly designed to deliver higher molecular weight compounds into skin. Here we show that a single topical application of pDNA-rIL10 in Lipoderm HMW was effective in decreasing mRNA levels of pro-inflammatory cytokines as well as reducing the recruitment of T-cells to IMQ-treated skin. Furthermore, this transcutaneous IL-10 gene therapy decreased signs of skin inflammation, reflected by reduced erythema. Moreover, the results provide an initial indication that IL10 may stimulate hair regrowth in psoriatic-like skin.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluating Methodological validity in the Analysis of Tai Chi and cognitive behavioral therapy for inflammation Reduction in Insomnia: A Letter to the Editor","authors":"Akiko Eto-Kimura , Shunsuke Yasuo , Yuki Kataoka","doi":"10.1016/j.bbi.2024.10.037","DOIUrl":"10.1016/j.bbi.2024.10.037","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In response to Eto-Kimura et al.","authors":"","doi":"10.1016/j.bbi.2024.10.038","DOIUrl":"https://doi.org/10.1016/j.bbi.2024.10.038","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Serology and Alzheimer's disease: Is infectious disease in the driver's seat?","authors":"A L Dawson, A A Willette","doi":"10.1016/j.bbi.2024.10.035","DOIUrl":"10.1016/j.bbi.2024.10.035","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Urvinder Kaur Sardarni, Anoop T Ambikan, Arpan Acharya, Samuel D Johnson, Sean N Avedissian, Ákos Végvári, Ujjwal Neogi, Siddappa N Byrareddy
{"title":"SARS-CoV-2 variants mediated tissue-specific metabolic reprogramming determines the disease pathophysiology in a hamster model.","authors":"Urvinder Kaur Sardarni, Anoop T Ambikan, Arpan Acharya, Samuel D Johnson, Sean N Avedissian, Ákos Végvári, Ujjwal Neogi, Siddappa N Byrareddy","doi":"10.1016/j.bbi.2024.10.032","DOIUrl":"10.1016/j.bbi.2024.10.032","url":null,"abstract":"<p><p>Despite significant effort, a clear understanding of host tissue-specific responses and their implications for immunopathogenicity against the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) variant infection has remained poorly defined. To shed light on the interaction between tissues and SARS-CoV-2 variants, we sought to characterize the complex relationship among acute multisystem manifestations, dysbiosis of the gut microbiota, and the resulting implications for SARS-CoV-2 variant-specific immunopathogenesis in the Golden Syrian Hamster (GSH) model using multi-omics approaches. Our investigation revealed the presence of increased SARS-CoV-2 genomic RNA in diverse tissues of delta-infected GSH compared to the omicron variant. Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders. Additionally, delta-infected GSH exhibited an altered fecal microbiota composition, marked by increased inflammation-associated taxa and reduced commensal bacteria compared to the omicron variant. These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rhonda L. McFleder , Thomas Musacchio , Johanna Keller , Susanne Knorr , Tobias Petschner , Jia Zhi Chen , Muthuraman Muthuraman , Mohammad Badr , Lisa Harder-Rauschenberger , Fabian Kremer , Selin Asci , Sophie Steinhauser , Ann-Kathrin Karl , Jonathan M. Brotchie , James B. Koprich , Jens Volkmann , Chi Wang Ip
{"title":"Deep brain stimulation halts Parkinson’s disease-related immune dysregulation in the brain and peripheral blood","authors":"Rhonda L. McFleder , Thomas Musacchio , Johanna Keller , Susanne Knorr , Tobias Petschner , Jia Zhi Chen , Muthuraman Muthuraman , Mohammad Badr , Lisa Harder-Rauschenberger , Fabian Kremer , Selin Asci , Sophie Steinhauser , Ann-Kathrin Karl , Jonathan M. Brotchie , James B. Koprich , Jens Volkmann , Chi Wang Ip","doi":"10.1016/j.bbi.2024.10.039","DOIUrl":"10.1016/j.bbi.2024.10.039","url":null,"abstract":"<div><div>Immune dysregulation in the brain and periphery is thought to contribute to the detrimental neurodegeneration that occurs in Parkinson’s disease (PD). Identifying mechanisms to reverse this dysregulation is key to developing disease-altering therapeutics for this currently incurable disease. Here we utilized the longitudinal data from the Parkinson’s Progression Marker Initiative to demonstrate that circulating lymphocytes progressively decline in PD and can be used to predict future motor symptom progression. Deep brain stimulation (DBS), which is used as a symptomatic treatment, could halt this progressive decline. By analyzing specific immune populations from a second cohort of patients, we could show that DBS causes a shift from the pro-inflammatory CD4<sup>+</sup> T helper 17 cells driving neurodegeneration to anti-inflammatory CD4<sup>+</sup> regulatory T cells. RNA-sequencing and immunohistochemistry in the brain of the A53T alpha-synuclein rat model of PD revealed that DBS also decreases neuroinflammation. These data suggest a potential disease-altering role for DBS by halting inflammatory processes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weiqing Jiang , Yitong He , Qianyu Liu , Shuyi Peng , Yanyan Ni , Xiali Zhong , Lan Guo
{"title":"Associations between childhood maltreatment, peripheral immune biomarkers, and psychiatric symptoms in adults: A cohort study of over 138,000 participants","authors":"Weiqing Jiang , Yitong He , Qianyu Liu , Shuyi Peng , Yanyan Ni , Xiali Zhong , Lan Guo","doi":"10.1016/j.bbi.2024.10.034","DOIUrl":"10.1016/j.bbi.2024.10.034","url":null,"abstract":"<div><h3>Background</h3><div>Few studies have integrated the impact of individual and cumulative childhood maltreatment on multiple psychiatric symptoms, with the mechanisms underlying these associations largely unknown. This study aims to comprehensively assess the associations between childhood maltreatment, multiple peripheral immune biomarkers, and various psychiatric symptoms in adulthood and to explore whether peripheral immune inflammation plays a mediator role in the associations between childhood maltreatment and psychiatric symptoms in adulthood.</div></div><div><h3>Methods</h3><div>Using data from the UK Biobank, we constructed a retrospective cohort study of 138,915 participants who provided self-reported childhood maltreatment and had peripheral immune biomarkers assessed. We examined seven types of psychiatric symptoms in adulthood, including depressive symptoms, anxiety symptoms, mania, post-traumatic stress disorder (PTSD), psychotic experiences, self-harm, and alcohol use disorder. Logistic regression models were performed to explore the associations between childhood maltreatment, immune biomarkers, and psychiatric symptoms, calculating the average marginal effects for each indicator of childhood maltreatment. Mediation analyses were conducted to determine the extent to which the immune biomarkers could explain the association between childhood maltreatment and psychiatric symptoms in adulthood. Subgroup and sensitivity analyses were also performed.</div></div><div><h3>Results</h3><div>Among the participants, 77,937 (56.10 %) were female, with a mean age of 55.91 (SD: 7.73) years at baseline. There were dose–response relationships existed between the accumulation of childhood maltreatment indicators and all seven assessed psychiatric symptoms and multimorbidity in adulthood (e.g., for depressive symptoms, OR = 1.67 [95 %CI, 1.57 to 1.78] for one childhood maltreatment indicator; OR = 2.77 [95 % CI, 2.58 to 2.97] for two; OR = 4.91 [95 % CI, 4.61 to 5.24] for three or more). Emotional abuse and physical neglect showed the strongest average marginal effects on psychiatric symptoms. Levels of C-reactive protein (CRP) and counts of leukocytes and neutrophils were positively associated with depressive symptoms (e.g., OR = 1.13 [95 % CI, 1.08 to 1.17] for CRP level), anxiety symptoms, PTSD, and psychotic experiences. Moreover, levels of CRP partially mediated the association between childhood maltreatment scores and psychiatric symptoms, albeit with a relatively low mediation proportion (0.65 %-1.77 %).</div></div><div><h3>Conclusions</h3><div>Our findings underscore the importance of interventions that address multiple forms of childhood maltreatment to mitigate long-term mental health challenges substantially. While peripheral immunity responses may serve as predictors of mental health problems, they might not to be the primary mechanism through which childhood maltreatment influences psychiatric symptoms in adulthood.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"mAbsolutely FABulous: From a case of mistaken identity to pinpoint precision in the antibodies formerly known as ‘VGKC’","authors":"Sophie N.M. Binks","doi":"10.1016/j.bbi.2024.10.040","DOIUrl":"10.1016/j.bbi.2024.10.040","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah R Vreijling, Brenda W J H Penninx, Josine E Verhoeven, Charlotte E Teunissen, Elena R Blujdea, Aartjan T F Beekman, Femke Lamers, Rick Jansen
{"title":"Running therapy or antidepressants as treatments for immunometabolic depression in patients with depressive and anxiety disorders: A secondary analysis of the MOTAR study.","authors":"Sarah R Vreijling, Brenda W J H Penninx, Josine E Verhoeven, Charlotte E Teunissen, Elena R Blujdea, Aartjan T F Beekman, Femke Lamers, Rick Jansen","doi":"10.1016/j.bbi.2024.10.033","DOIUrl":"10.1016/j.bbi.2024.10.033","url":null,"abstract":"<p><strong>Background: </strong>Exercise promotes immunometabolic health and is increasingly recognized as an effective depression treatment. Exercise may be beneficial for patients with immunometabolic depression (IMD), who experience inflammatory and metabolic dysregulations and may respond less to antidepressants. This secondary analysis of the MOTAR study compared the effects of running therapy and antidepressants on IMD features among patients with depression and/or anxiety disorder. We additionally assessed whether baseline IMD moderated intervention effects on depression.</p><p><strong>Methods: </strong>Participants received 16 weeks of group-based running therapy (N = 96) or escitalopram/sertraline (N = 45) in a partially randomized patient preference design. IMD features included atypical, energy-related symptom (AES) severity, inflammation index (CRP, IFN-γ, IL-6, TNF-α), metabolic syndrome index, three metabolite principle components (PC) (derived from 73 metabolites) and a composite IMD index.</p><p><strong>Results: </strong>Interventions differed in changes in the metabolic syndrome index (d = 0.59, p = 0.026) and IMD index (d = 0.85, p < 0.001). While running therapy decreased both outcomes, the antidepressant group showed an increased IMD index. Although groups did not differ statistically significant in changes in AES severity, inflammation index, and metabolite PC1, results indicated a consistent trend towards greater improvement with running therapy across these outcomes as well (d = 0.38 to 0.52). Baseline IMD did not moderate intervention effects on depression outcomes.</p><p><strong>Conclusions: </strong>This study suggests that exercise more effectively targets the IMD dimension than antidepressants. Patients with IMD did not benefit more from running therapy than antidepressants in terms of reductions in depression. Exercise should be considered an alternative or complementary treatment to particularly reduce IMD features in depressed patients.</p><p><strong>Trial registration: </strong>Trialregister.nl Number of identification: NTR3460.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}