Pub Date : 2024-10-25DOI: 10.1016/j.bbih.2024.100894
Mariana Conceição , Leonardo Delello Di Filippo , Jonatas Lobato Duarte , Fernando Pereira Beserra , Maria Palmira Daflon Gremião , Marlus Chorilli
Drug repurposing, also known as drug repositioning, involves identifying new applications for drugs whose effects in a disease are already established. Doxycycline, a broad-spectrum antibiotic belonging to the tetracycline class, has demonstrated potential activity against neurodegenerative diseases like Alzheimer's and Parkinson's. However, despite its promise, the repurposed use of doxycycline encounters challenges in reaching the brain in adequate concentrations to exert its effects. To address this issue, nanostructured systems offer an innovative approach that can enhance brain targeting and the desired therapeutic outcomes. This review discusses the advances in doxycycline repurposing for Alzheimer's disease, presenting physicochemical and biological aspects that permeate doxycycline's repositioning and its application in nano-based delivery systems.
{"title":"Repurposing doxycycline for Alzheimer's treatment: Challenges from a nano-based drug delivery perspective","authors":"Mariana Conceição , Leonardo Delello Di Filippo , Jonatas Lobato Duarte , Fernando Pereira Beserra , Maria Palmira Daflon Gremião , Marlus Chorilli","doi":"10.1016/j.bbih.2024.100894","DOIUrl":"10.1016/j.bbih.2024.100894","url":null,"abstract":"<div><div>Drug repurposing, also known as drug repositioning, involves identifying new applications for drugs whose effects in a disease are already established. Doxycycline, a broad-spectrum antibiotic belonging to the tetracycline class, has demonstrated potential activity against neurodegenerative diseases like Alzheimer's and Parkinson's. However, despite its promise, the repurposed use of doxycycline encounters challenges in reaching the brain in adequate concentrations to exert its effects. To address this issue, nanostructured systems offer an innovative approach that can enhance brain targeting and the desired therapeutic outcomes. This review discusses the advances in doxycycline repurposing for Alzheimer's disease, presenting physicochemical and biological aspects that permeate doxycycline's repositioning and its application in nano-based delivery systems.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100894"},"PeriodicalIF":3.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1016/j.bbih.2024.100893
Yating Luo , Sha Wang , Qinqin Cheng , Jing Li , Huiyi Zhang , Jingying Wang , Juan Luo , Chen Pan , Qiuxiang Zhang , Jianfei Xie , Andy S.K. Cheng
Background
In the low-resource rural areas, older adults may experience prolonged and severe depressive symptoms. This study aimed to investigate the relationship between uric acid, depressive symptoms and immunoinflammatory among rural older adults.
Method
This case-control study was conducted in 17 rural villages in Hunan Province, China, between January 2023 and April 2024. This study included 180 participants: (1) Rural Older Adults with Depressive Symptoms group:90 patients with first-time diagnosed with depressive symptoms (Geriatric Depression Scale-15, GDS-15 ≥ 5 scores); (2) Control group: 90 individually matched (age and sex) healthy subjects (GDS-15 < 5 scores) who were aged ≥60 years.
Results
Both males and females, depressive symptoms were associated with higher uric acid levels and C-reactive protein levels (All P < 0.05). Whereas in females, depressive symptoms were also linked to higher procalcitonin (P = 0.005) and serum amyloid A (P = 0.008) levels. In addition, C-reactive protein plays a significant mediating role between uric acid and depressive symptoms in males.
Conclusion
Further investigation is necessary to clarify the underlying mechanisms, examine gender-specific disparities, and assess potential therapeutic interventions targeting uric acid and inflammation levels to mitigate mental disorders risk.
{"title":"Associations between uric acid and depressive symptoms, and the mediating role of immunoinflammatory: Findings from rural older adults","authors":"Yating Luo , Sha Wang , Qinqin Cheng , Jing Li , Huiyi Zhang , Jingying Wang , Juan Luo , Chen Pan , Qiuxiang Zhang , Jianfei Xie , Andy S.K. Cheng","doi":"10.1016/j.bbih.2024.100893","DOIUrl":"10.1016/j.bbih.2024.100893","url":null,"abstract":"<div><h3>Background</h3><div>In the low-resource rural areas, older adults may experience prolonged and severe depressive symptoms. This study aimed to investigate the relationship between uric acid, depressive symptoms and immunoinflammatory among rural older adults.</div></div><div><h3>Method</h3><div>This case-control study was conducted in 17 rural villages in Hunan Province, China, between January 2023 and April 2024. This study included 180 participants: (1) Rural Older Adults with Depressive Symptoms group:90 patients with first-time diagnosed with depressive symptoms (Geriatric Depression Scale-15, GDS-15 ≥ 5 scores); (2) Control group: 90 individually matched (age and sex) healthy subjects (GDS-15 < 5 scores) who were aged ≥60 years.</div></div><div><h3>Results</h3><div>Both males and females, depressive symptoms were associated with higher uric acid levels and C-reactive protein levels (All <em>P</em> < 0.05). Whereas in females, depressive symptoms were also linked to higher procalcitonin (<em>P</em> = 0.005) and serum amyloid A (<em>P</em> = 0.008) levels. In addition, C-reactive protein plays a significant mediating role between uric acid and depressive symptoms in males.</div></div><div><h3>Conclusion</h3><div>Further investigation is necessary to clarify the underlying mechanisms, examine gender-specific disparities, and assess potential therapeutic interventions targeting uric acid and inflammation levels to mitigate mental disorders risk.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100893"},"PeriodicalIF":3.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.bbih.2024.100889
Xiao-Lei Shen , Yu-Han Jiang , Shen-Jie Li, Xin-Yi Xie, Yu Cheng, Li Wu, Jun Shen, Wei Chen, Jian-Ren Liu
Background
Patients with coronavirus disease 2019(COVID-2019) infections may still experience long-term effects, with fatigue being one of the most frequent ones. Clinical research on the long COVID in the Chinese population after infection is comparatively lacking.
Objective
To collect and analyze the long-term effects of non-severe COVID-19 infection patients and to develop a model for the prediction of fatigue symptoms.
Methods
223 non-severe COVID-19 patients admitted to one designated hospital were enrolled after finish all the self-designed clinical information registration form and nine-month follow-up. We explored the frequency and symptom types of long COVID. Correlation analysis was done on the neuropsychological scale results. After cluster analysis, lasoo regression and logistic regressions, a nomogram prediction model was produced as a result of investigating the risk factors for fatigue.
Results
A total of 108 (48.4%) of the 223 non-severe COVID-19 patients reported sequelae for more than 4 weeks, and of these, 35 (15.7%) had fatigue sequelae that were scale-confirmed. Other sequelae of more than 10% were brain fog (n = 37,16.6%), cough (n = 26,11.7%) and insomnia (n = 23,10.3%). A correlation between depression and fatigue was discovered following the completion of neuropsychological scale. The duration of hospitalization, the non-use of antiviral medications in treatment, IL-6 and CD16+CD56+ cell levels in blood are the main independent risk factors and predictors of fatigue sequelae in long COVID. Additionally, the neurology diseases and vaccination status may also influence the fatigue sequelae.
Conclusion
Nearly half of the patients infected with COVID-19 Omicron variant complained of sequelae, and fatigue was the most common symptom, which was correlated with depression. Significant predictors of fatigue sequelae included length of hospitalization, non-use of antiviral drug, and immune-related serum markers of IL-6 and CD16+CD56+ NK cell levels. The presence of neurology diseases and a lack of vaccination could also predict the occurrence of fatigue sequelae.
{"title":"Clinical features and predictive nomogram for fatigue sequelae in non-severe patients infected with SARS-CoV-2 Omicron variant in Shanghai, China","authors":"Xiao-Lei Shen , Yu-Han Jiang , Shen-Jie Li, Xin-Yi Xie, Yu Cheng, Li Wu, Jun Shen, Wei Chen, Jian-Ren Liu","doi":"10.1016/j.bbih.2024.100889","DOIUrl":"10.1016/j.bbih.2024.100889","url":null,"abstract":"<div><h3>Background</h3><div>Patients with coronavirus disease 2019(COVID-2019) infections may still experience long-term effects, with fatigue being one of the most frequent ones. Clinical research on the long COVID in the Chinese population after infection is comparatively lacking.</div></div><div><h3>Objective</h3><div>To collect and analyze the long-term effects of non-severe COVID-19 infection patients and to develop a model for the prediction of fatigue symptoms.</div></div><div><h3>Methods</h3><div>223 non-severe COVID-19 patients admitted to one designated hospital were enrolled after finish all the self-designed clinical information registration form and nine-month follow-up. We explored the frequency and symptom types of long COVID. Correlation analysis was done on the neuropsychological scale results. After cluster analysis, lasoo regression and logistic regressions, a nomogram prediction model was produced as a result of investigating the risk factors for fatigue.</div></div><div><h3>Results</h3><div>A total of 108 (48.4%) of the 223 non-severe COVID-19 patients reported sequelae for more than 4 weeks, and of these, 35 (15.7%) had fatigue sequelae that were scale-confirmed. Other sequelae of more than 10% were brain fog (<em>n</em> = 37,16.6%), cough (<em>n</em> = 26,11.7%) and insomnia (n = 23,10.3%). A correlation between depression and fatigue was discovered following the completion of neuropsychological scale. The duration of hospitalization, the non-use of antiviral medications in treatment, IL-6 and CD16+CD56<sup>+</sup> cell levels in blood are the main independent risk factors and predictors of fatigue sequelae in long COVID. Additionally, the neurology diseases and vaccination status may also influence the fatigue sequelae.</div></div><div><h3>Conclusion</h3><div>Nearly half of the patients infected with COVID-19 Omicron variant complained of sequelae, and fatigue was the most common symptom, which was correlated with depression. Significant predictors of fatigue sequelae included length of hospitalization, non-use of antiviral drug, and immune-related serum markers of IL-6 and CD16+CD56<sup>+</sup> NK cell levels. The presence of neurology diseases and a lack of vaccination could also predict the occurrence of fatigue sequelae.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100889"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.bbih.2024.100874
Sara A. Norton , Lauren M. Blaydon , Megan Niehaus , Alex P. Miller , Patrick L. Hill , Thomas F. Oltmanns , Ryan Bogdan
Introduction
Increasing evidence suggests that inflammation may play a pivotal role in the development of chronic pain and fatigue in aging individuals. This study investigated the relationship between three inflammatory markers (IL-6, CRP, and TNFα) and pain and fatigue, both cross-sectionally and longitudinally, in a sample of older adults from the Saint Louis Personality and Aging (SPAN) study.
Methods
SPAN study participants provided blood samples at two in-person sessions approximately 2 years apart for the analysis of the inflammatory biomarkers IL-6, CRP, and TNFα. Pain and fatigue were assessed using the RAND-36 Health Status Inventory. Correlations (with false discovery rate correction for multiple testing) and follow-up linear regressions including potentially confounding demographic (e.g., annual household income) and health (e.g., BMI, medication use) covariates were used to estimate cross sectional and longitudinal associations. Analytic ns ranged from 533 to 815.
Results
Cross-sectional analyses revealed that higher IL-6 and CRP were associated with greater reported pain and fatigue, even after accounting for covariates (βs > .098, ps < .05). TNFα was associated with greater fatigue only (β = .100, p = .012). Longitudinally, CRP and IL-6 predicted future pain and fatigue, although only the relationship between CRP and future fatigue survived the inclusion of covariates (β = .104, p = .022). Both pain and fatigue predicted higher levels of IL-6 and CRP approximately 2 years later, although only the associations with IL-6 survived the inclusion of covariates (βs > .12, ps < .01).
Discussion
Our study adds to a growing body of literature showing that inflammation is associated with greater pain and fatigue in older adults. Our longitudinal data showing temporal bidirectional associations is consistent with evidence from non-human animal models that heightened inflammation causally contributes to fatigue and also suggests that the experience of pain and fatigue may contribute to inflammation. It will be important for future work to identify how lifestyle factors associated with pain and fatigue (e.g., physical activity) may contribute to these associations.
{"title":"Inflammation is associated with pain and fatigue in older adults","authors":"Sara A. Norton , Lauren M. Blaydon , Megan Niehaus , Alex P. Miller , Patrick L. Hill , Thomas F. Oltmanns , Ryan Bogdan","doi":"10.1016/j.bbih.2024.100874","DOIUrl":"10.1016/j.bbih.2024.100874","url":null,"abstract":"<div><h3>Introduction</h3><div>Increasing evidence suggests that inflammation may play a pivotal role in the development of chronic pain and fatigue in aging individuals. This study investigated the relationship between three inflammatory markers (IL-6, CRP, and TNFα) and pain and fatigue, both cross-sectionally and longitudinally, in a sample of older adults from the Saint Louis Personality and Aging (SPAN) study.</div></div><div><h3>Methods</h3><div>SPAN study participants provided blood samples at two in-person sessions approximately 2 years apart for the analysis of the inflammatory biomarkers IL-6, CRP, and TNFα. Pain and fatigue were assessed using the RAND-36 Health Status Inventory. Correlations (with false discovery rate correction for multiple testing) and follow-up linear regressions including potentially confounding demographic (e.g., annual household income) and health (e.g., BMI, medication use) covariates were used to estimate cross sectional and longitudinal associations. Analytic ns ranged from 533 to 815.</div></div><div><h3>Results</h3><div>Cross-sectional analyses revealed that higher IL-6 and CRP were associated with greater reported pain and fatigue, even after accounting for covariates (βs > .098, <em>p</em>s < .05). TNFα was associated with greater fatigue only (β = .100, <em>p</em> = .012). Longitudinally, CRP and IL-6 predicted future pain and fatigue, although only the relationship between CRP and future fatigue survived the inclusion of covariates (β = .104, <em>p</em> = .022). Both pain and fatigue predicted higher levels of IL-6 and CRP approximately 2 years later, although only the associations with IL-6 survived the inclusion of covariates (βs > .12, <em>ps</em> < .01).</div></div><div><h3>Discussion</h3><div>Our study adds to a growing body of literature showing that inflammation is associated with greater pain and fatigue in older adults. Our longitudinal data showing temporal bidirectional associations is consistent with evidence from non-human animal models that heightened inflammation causally contributes to fatigue and also suggests that the experience of pain and fatigue may contribute to inflammation. It will be important for future work to identify how lifestyle factors associated with pain and fatigue (e.g., physical activity) may contribute to these associations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100874"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.bbih.2024.100890
Beibei Xu , Hao Li , He Zheng , Zhongyu Gao , Zhigang Miao , Xingshun Xu , Hao Yang , Yi Yang
Interleukin 18 (IL-18), a proinflammatory cytokine, has been implicated in various neurological disorders, including cerebrovascular disease and psychiatric disorders. In a previous study, IL-18 was observed to activate microglia and enhance the inflammatory response following intracranial hemorrhage (ICH). However, the underlying mechanism remains unclear. In the present study, we found that IL-18 and IL-18 receptor (IL-18 R) are primarily secreted by neurons during the early stages after ICH, with microglia becoming the predominant source at 12–24 h after ICH. Meanwhile, the expression level of IL-18 R increased following ICH, along with an augmentation in the binding affinity of IL-18 R to IL-18. Subsequently, the deficiency of IL-18 R mitigated neurological impairment and subsequent activation of inflammatory pathways in mice post-ICH. Moreover, our findings suggest that IL-18-induced neurological injury after ICH may be mediated by the interaction between IL18R and NKCC1. Significantly, the NKCC1 inhibitor rescued the neurologic injury after ICH. In conclusion, our study suggests that targeting the IL-18/IL-18R/NKCC1 pathway could be an effective therapeutic strategy to attenuate secondary brain injury after ICH.
白细胞介素 18（IL-18）是一种促炎细胞因子，与包括脑血管疾病和精神疾病在内的多种神经系统疾病有关。之前的一项研究观察到，IL-18 能激活小胶质细胞并增强颅内出血（ICH）后的炎症反应。然而，其潜在机制仍不清楚。本研究发现，在 ICH 后的早期阶段，IL-18 和 IL-18 受体（IL-18 R）主要由神经元分泌，而在 ICH 后 12-24 h，小胶质细胞成为主要来源。同时，IL-18 R 在 ICH 后的表达水平升高，IL-18 R 与 IL-18 的结合亲和力增强。随后，IL-18 R的缺乏减轻了ICH后小鼠的神经功能损伤和随后的炎症通路激活。此外，我们的研究结果表明，IL-18 诱导的 ICH 后神经损伤可能是由 IL18R 和 NKCC1 之间的相互作用介导的。值得注意的是，NKCC1 抑制剂能挽救 ICH 后的神经损伤。总之，我们的研究表明，靶向 IL-18/IL-18R/NKCC1 通路可能是减轻 ICH 后继发性脑损伤的有效治疗策略。
{"title":"Interleukin-18 interacts with NKCC1 to mediate brain injury after intracerebral hemorrhage","authors":"Beibei Xu , Hao Li , He Zheng , Zhongyu Gao , Zhigang Miao , Xingshun Xu , Hao Yang , Yi Yang","doi":"10.1016/j.bbih.2024.100890","DOIUrl":"10.1016/j.bbih.2024.100890","url":null,"abstract":"<div><div>Interleukin 18 (IL-18), a proinflammatory cytokine, has been implicated in various neurological disorders, including cerebrovascular disease and psychiatric disorders. In a previous study, IL-18 was observed to activate microglia and enhance the inflammatory response following intracranial hemorrhage (ICH). However, the underlying mechanism remains unclear. In the present study, we found that IL-18 and IL-18 receptor (IL-18 R) are primarily secreted by neurons during the early stages after ICH, with microglia becoming the predominant source at 12–24 h after ICH. Meanwhile, the expression level of IL-18 R increased following ICH, along with an augmentation in the binding affinity of IL-18 R to IL-18. Subsequently, the deficiency of IL-18 R mitigated neurological impairment and subsequent activation of inflammatory pathways in mice post-ICH. Moreover, our findings suggest that IL-18-induced neurological injury after ICH may be mediated by the interaction between IL18R and NKCC1. Significantly, the NKCC1 inhibitor rescued the neurologic injury after ICH. In conclusion, our study suggests that targeting the IL-18/IL-18R/NKCC1 pathway could be an effective therapeutic strategy to attenuate secondary brain injury after ICH.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100890"},"PeriodicalIF":3.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.bbih.2024.100892
Shannon K. Murphy , Madeline R. Pike , Emily Lipner , Seth D. Maxwell , Barbara A. Cohn , Piera Cirillo , Nickilou Y. Krigbaum , Elizabeth C. Breen , Lauren M. Ellman
Objectives
To determine if maternal prenatal infection increases risk of offspring postnatal infections through age 5 or diagnosis of respiratory allergy at age 5, independent of prenatal/postnatal antibiotic exposure. To evaluate if frequency of offspring infections mediates an association between prenatal infection and respiratory allergy at age 5.
Study design
Secondary data analyses were performed from the Child Health and Development Studies (CHDS), a prospective, longitudinal birth cohort that enrolled pregnant women from 1959 to 1966 (N = 19,044 live births). The sample included a subset of mother-offspring dyads (n = 2062) with abstracted medical record data from the prenatal period through age 5 that included information on antibiotic use, infection, and offspring respiratory allergy.
Results
Second trimester maternal infection was associated with an increased risk of offspring infection (IRR = 1.23; 95% CI = 1.09–1.39; p = 0.001). No significant direct associations were detected between prenatal infection and diagnosis of offspring respiratory allergy. Offspring infection (OR = 1.17; 95% CI = 1.13–1.20; p < 0.001) and antibiotic exposure (OR = 1.28; 95% CI = 1.22–1.33; p < 0.001) were significantly associated with a diagnosis of offspring respiratory allergy. Respiratory allergy diagnosis risk was greater with increasing offspring infection exposure and antibiotics. There was a significant indirect effect of second trimester maternal infection on offspring respiratory allergy, due to infections and not antibiotic use, via offspring infection, indicating a partially mediated effect.
Conclusion
Prenatal maternal infection may contribute to increase risk for early childhood infections, which in turn, may increase risk for allergic conditions.
目的确定母体产前感染是否会增加后代5岁前的产后感染风险或5岁时诊断出呼吸道过敏的风险，而与产前/产后抗生素暴露无关。研究设计对儿童健康与发展研究（Child Health and Development Studies，CHDS）的二次数据进行了分析，该研究是一项前瞻性纵向出生队列研究，从 1959 年到 1966 年对孕妇进行了登记（N = 19,044 例活产）。样本包括母子二人组（n = 2062）的子集，这些子集具有从产前到 5 岁的病历摘要数据，其中包括抗生素使用、感染和后代呼吸道过敏的信息。产前感染与后代呼吸道过敏诊断之间未发现明显的直接关联。后代感染（OR = 1.17; 95% CI = 1.13-1.20; p <0.001）和抗生素暴露（OR = 1.28; 95% CI = 1.22-1.33; p <0.001）与后代呼吸道过敏诊断显著相关。呼吸道过敏诊断风险随后代感染暴露和抗生素的增加而增加。第二孕期母体感染对后代呼吸道过敏有明显的间接影响，这是由于感染而不是抗生素的使用，通过后代感染而产生的，这表明存在部分中介效应。
{"title":"Contributions of maternal prenatal infection and antibiotic exposure to offspring infection and risk for allergic respiratory conditions through age 5","authors":"Shannon K. Murphy , Madeline R. Pike , Emily Lipner , Seth D. Maxwell , Barbara A. Cohn , Piera Cirillo , Nickilou Y. Krigbaum , Elizabeth C. Breen , Lauren M. Ellman","doi":"10.1016/j.bbih.2024.100892","DOIUrl":"10.1016/j.bbih.2024.100892","url":null,"abstract":"<div><h3>Objectives</h3><div>To determine if maternal prenatal infection increases risk of offspring postnatal infections through age 5 or diagnosis of respiratory allergy at age 5, independent of prenatal/postnatal antibiotic exposure. To evaluate if frequency of offspring infections mediates an association between prenatal infection and respiratory allergy at age 5.</div></div><div><h3>Study design</h3><div>Secondary data analyses were performed from the Child Health and Development Studies (CHDS), a prospective, longitudinal birth cohort that enrolled pregnant women from 1959 to 1966 (N = 19,044 live births). The sample included a subset of mother-offspring dyads (<em>n</em> = 2062) with abstracted medical record data from the prenatal period through age 5 that included information on antibiotic use, infection, and offspring respiratory allergy.</div></div><div><h3>Results</h3><div>Second trimester maternal infection was associated with an increased risk of offspring infection (IRR = 1.23; 95% CI = 1.09–1.39; <em>p</em> = 0.001). No significant direct associations were detected between prenatal infection and diagnosis of offspring respiratory allergy. Offspring infection (OR = 1.17; 95% CI = 1.13–1.20; <em>p</em> < 0.001) and antibiotic exposure (OR = 1.28; 95% CI = 1.22–1.33; <em>p</em> < 0.001) were significantly associated with a diagnosis of offspring respiratory allergy. Respiratory allergy diagnosis risk was greater with increasing offspring infection exposure and antibiotics. There was a significant indirect effect of second trimester maternal infection on offspring respiratory allergy, due to infections and not antibiotic use, via offspring infection, indicating a partially mediated effect.</div></div><div><h3>Conclusion</h3><div>Prenatal maternal infection may contribute to increase risk for early childhood infections, which in turn, may increase risk for allergic conditions.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100892"},"PeriodicalIF":3.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1016/j.bbih.2024.100888
Echo Yongqi Luo , Raymond Chuen-Chung Chang , Javier Gilbert-Jaramillo
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic. After the success of therapeutics and worldwide vaccination, the long-term sequelae of SARS-CoV-2 infections are yet to be determined. Common symptoms of COVID-19 include the loss of taste and smell, suggesting SARS-CoV-2 infection has a potentially detrimental effect on neurons within the olfactory/taste pathways, with direct access to the central nervous system (CNS). This could explain the detection of SARS-CoV-2 antigens in the brains of COVID-19 patients. Different viruses display neurotropism that causes impaired neurodevelopment and/or neurodegeneration. Hence, it is plausible that COVID-19-associated neuropathologies are directly driven by SARS-CoV-2 infection in the CNS. Microglia, resident immune cells of the brain, are constantly under investigation as their surveillance role has been suggested to act as a friend or a foe impacting the progression of neurological disorders. Herein, we review the current literature suggesting microglia potentially been a susceptible target by SARS-CoV-2 virions and their role in viral dissemination within the CNS. Particular attention is given to the different experimental models and their translational potential.
{"title":"SARS-CoV-2 infection in microglia and its sequelae: What do we know so far?","authors":"Echo Yongqi Luo , Raymond Chuen-Chung Chang , Javier Gilbert-Jaramillo","doi":"10.1016/j.bbih.2024.100888","DOIUrl":"10.1016/j.bbih.2024.100888","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic. After the success of therapeutics and worldwide vaccination, the long-term sequelae of SARS-CoV-2 infections are yet to be determined. Common symptoms of COVID-19 include the loss of taste and smell, suggesting SARS-CoV-2 infection has a potentially detrimental effect on neurons within the olfactory/taste pathways, with direct access to the central nervous system (CNS). This could explain the detection of SARS-CoV-2 antigens in the brains of COVID-19 patients. Different viruses display neurotropism that causes impaired neurodevelopment and/or neurodegeneration. Hence, it is plausible that COVID-19-associated neuropathologies are directly driven by SARS-CoV-2 infection in the CNS. Microglia, resident immune cells of the brain, are constantly under investigation as their surveillance role has been suggested to act as a friend or a foe impacting the progression of neurological disorders. Herein, we review the current literature suggesting microglia potentially been a susceptible target by SARS-CoV-2 virions and their role in viral dissemination within the CNS. Particular attention is given to the different experimental models and their translational potential.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100888"},"PeriodicalIF":3.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.bbih.2024.100891
J.D. Tingling , S.A. Krauklis , P.L. Haak , R. Carr , A.Y. Louie , R.W. Johnson , A.J. Steelman
Respiratory infection by influenza A virus (IAV) is known to cause systemic inflammation, neuroinflammation, and cognitive impairment. We previously found that experimental infection with IAV affected oligodendrocyte homeostasis, which was associated with altered expression of genes involved in myelin maintenance as well as the lipidome. In this study, we sought to determine if clemastine, an antihistamine with myelin promoting properties, could reverse the effects of IAV on oligodendrocyte (OL) specific genes, as well as mitigate infection-induced cognitive impairment. Male and female C57BL/6J mice were randomized into experimental groups based on clemastine treatment, infection, and sex. Treatment with vehicle or clemastine (10mg/kg/d) commenced seven days prior to inoculation with either saline or IAV and continued throughout the experiment. Body weight was measured throughout the infection. Spatial learning and memory were assessed by Morris water maze. Sickness behavior was assessed by measuring burrowing response. Immune cell responses were determined by flow cytometry, RT-qPCR, antigen recall assays and ELISA, and viral load assessed by RT-qPCR. Hippocampal levels of neuroinflammatory (Tnf, Cdkn1a) and myelin (Plp1, Mag, Ugt8a) genes were determined by RT-qPCR. Mice infected with IAV developed weight loss, impaired cognitive flexibility, reduced burrowing behavior, altered lung immune cell infiltration, increased circulating anti-viral IgM and IgG levels and increased T cell responses to IAV epitopes. Infection increased hippocampal levels of genes associated with neuroinflammation and decreased levels of genes involved in myelination. Clemastine treatment resulted in earlier recovery of weight loss in males and increased IgM levels for both sexes, but neither affected expression levels of Tnf or Cdkn1a, nor rescued changes to oligodendrocyte genes. However, treatment mitigated infection-induced neurocognitive impairment.
{"title":"Prophylactic clemastine treatment improves influenza A virus-induced cognitive dysfunction in mice.","authors":"J.D. Tingling , S.A. Krauklis , P.L. Haak , R. Carr , A.Y. Louie , R.W. Johnson , A.J. Steelman","doi":"10.1016/j.bbih.2024.100891","DOIUrl":"10.1016/j.bbih.2024.100891","url":null,"abstract":"<div><div>Respiratory infection by influenza A virus (IAV) is known to cause systemic inflammation, neuroinflammation, and cognitive impairment. We previously found that experimental infection with IAV affected oligodendrocyte homeostasis, which was associated with altered expression of genes involved in myelin maintenance as well as the lipidome. In this study, we sought to determine if clemastine, an antihistamine with myelin promoting properties, could reverse the effects of IAV on oligodendrocyte (OL) specific genes, as well as mitigate infection-induced cognitive impairment. Male and female C57BL/6J mice were randomized into experimental groups based on clemastine treatment, infection, and sex. Treatment with vehicle or clemastine (10mg/kg/d) commenced seven days prior to inoculation with either saline or IAV and continued throughout the experiment. Body weight was measured throughout the infection. Spatial learning and memory were assessed by Morris water maze. Sickness behavior was assessed by measuring burrowing response. Immune cell responses were determined by flow cytometry, RT-qPCR, antigen recall assays and ELISA, and viral load assessed by RT-qPCR. Hippocampal levels of neuroinflammatory (<em>Tnf, Cdkn1a</em>) and myelin (<em>Plp1</em>, <em>Mag</em>, <em>Ugt8a</em>) genes were determined by RT-qPCR. Mice infected with IAV developed weight loss, impaired cognitive flexibility, reduced burrowing behavior, altered lung immune cell infiltration, increased circulating anti-viral IgM and IgG levels and increased T cell responses to IAV epitopes. Infection increased hippocampal levels of genes associated with neuroinflammation and decreased levels of genes involved in myelination. Clemastine treatment resulted in earlier recovery of weight loss in males and increased IgM levels for both sexes, but neither affected expression levels of <em>Tnf</em> or <em>Cdkn1a</em>, nor rescued changes to oligodendrocyte genes. However, treatment mitigated infection-induced neurocognitive impairment.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100891"},"PeriodicalIF":3.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-06DOI: 10.1016/j.bbih.2024.100887
Liza Mekschrat , Michael Göring , Bjarne Schmalbach , Nicolas Rohleder , Katja Petrowski
Light influences circadian rhythms, including that of the stress hormone cortisol. Cortisol, in turn, has been observed to promote expression of the anti-inflammatory cytokine IL-10. It is thus of interest whether the cytokine IL-10 is also influenced by light, perhaps in accord with the diurnal variations in cortisol. Hence, this highly standardized preliminary sleep laboratory study in healthy adult men investigated a potential influence of different light exposure on IL-10 and cortisol concentrations in blood. In a between-subject design, N = 42 participants were exposed to either bright, dim, blue or red light after wake-up. Two mixed-model analyses with the factors of light condition and time (across eight IL-10 and cortisol sampling points) were conducted. Additionally, area under the curve measurements (AUCg and AUCi) were calculated for both cortisol and IL-10. Across all conditions, IL-10 and cortisol concentrations significantly changed over time. However, none of the light conditions exerted a greater influence on IL-10 or cortisol levels than others. For cortisol, there was greater total output (AUCg) in the blue-light condition in particular. Further research is needed to gain insight into whether or not types of light or cortisol levels have a hand in influencing natural IL-10 concentrations.
{"title":"The influence of light on Interleukin-10: A preliminary study","authors":"Liza Mekschrat , Michael Göring , Bjarne Schmalbach , Nicolas Rohleder , Katja Petrowski","doi":"10.1016/j.bbih.2024.100887","DOIUrl":"10.1016/j.bbih.2024.100887","url":null,"abstract":"<div><div>Light influences circadian rhythms, including that of the stress hormone cortisol. Cortisol, in turn, has been observed to promote expression of the anti-inflammatory cytokine IL-10. It is thus of interest whether the cytokine IL-10 is also influenced by light, perhaps in accord with the diurnal variations in cortisol. Hence, this highly standardized preliminary sleep laboratory study in healthy adult men investigated a potential influence of different light exposure on IL-10 and cortisol concentrations in blood. In a between-subject design, <em>N</em> = 42 participants were exposed to either bright, dim, blue or red light after wake-up. Two mixed-model analyses with the factors of light condition and time (across eight IL-10 and cortisol sampling points) were conducted. Additionally, area under the curve measurements (AUCg and AUCi) were calculated for both cortisol and IL-10. Across all conditions, IL-10 and cortisol concentrations significantly changed over time. However, none of the light conditions exerted a greater influence on IL-10 or cortisol levels than others. For cortisol, there was greater total output (AUCg) in the blue-light condition in particular. Further research is needed to gain insight into whether or not types of light or cortisol levels have a hand in influencing natural IL-10 concentrations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100887"},"PeriodicalIF":3.7,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1016/j.bbih.2024.100885
Claudio Singh Solorzano , Marta Spinoni , Maria Grazia Di Benedetto , Alessandra Biaggi , Moira Marizzoni , Elena Gatti , Cristina Festari , Michela Pievani , Caterina Grano , Annamaria Cattaneo
Objective
An emerging marker of depression in the perinatal period is represented by a reduction in the autonomic nervous system (ANS) activity, reflected by heart rate variability (HRV). This scoping review aims to map the association between HRV and depression during the perinatal period and to understand its potential clinical implications.
Introduction
Previous evidence associated ANS dysfunction and depressive symptomatology in the general population. Few observational and intervention studies investigated how HRV could be related to both pre- and post-partum depressive symptoms. However, high heterogeneity in the study designs and methods has been reported. Therefore, this scoping review plans to combine all these findings to build a starting point for future research.
Inclusion criteria
This scoping review will consider articles focusing on the association between HRV and depression in the peripartum and – when available – on the impact of interventions on HRV and how this correlates with changes in depressive symptoms. Studies will be included with no restrictions on participants’ age, peripartum time points for the assessment, and HRV parameters collected.
Methods
We will perform a systematic search using the Medline (PubMed), PsychInfo, and Web of Science (WoS) databases. Two authors will independently screen titles, abstracts, and then full-text articles that meet the inclusion criteria. The review will include only journal articles published in English, with no time limitations. Data will be extracted and presented in tables and/or graphical representations to summarise and describe the results. Extracted data will be reported in a comprehensive summary.
目的 围产期抑郁症的一个新标志是自律神经系统（ANS）活动的减少，这反映在心率变异性（HRV）上。本范围综述旨在描绘围产期心率变异与抑郁之间的关系，并了解其潜在的临床意义。很少有观察性和干预性研究调查心率变异与产前和产后抑郁症状的关系。然而，研究设计和方法的异质性很高。因此，本范围界定综述计划将所有这些研究结果结合起来，为今后的研究提供一个起点。纳入标准本范围界定综述将考虑关注围产期心率变异与抑郁症之间关系的文章，以及（如果有的话）关注干预措施对心率变异的影响以及这种影响如何与抑郁症状的变化相关联的文章。我们将使用 Medline (PubMed)、PsychInfo 和 Web of Science (WoS) 数据库进行系统检索。两位作者将独立筛选符合纳入标准的文章标题、摘要和全文。综述只包括以英文发表的期刊文章，没有时间限制。提取的数据将以表格和/或图表的形式呈现，以总结和描述结果。提取的数据将以综合摘要的形式报告。
{"title":"Heart rate variability and perinatal depressive symptoms: A scoping review protocol","authors":"Claudio Singh Solorzano , Marta Spinoni , Maria Grazia Di Benedetto , Alessandra Biaggi , Moira Marizzoni , Elena Gatti , Cristina Festari , Michela Pievani , Caterina Grano , Annamaria Cattaneo","doi":"10.1016/j.bbih.2024.100885","DOIUrl":"10.1016/j.bbih.2024.100885","url":null,"abstract":"<div><h3>Objective</h3><div>An emerging marker of depression in the perinatal period is represented by a reduction in the autonomic nervous system (ANS) activity, reflected by heart rate variability (HRV). This scoping review aims to map the association between HRV and depression during the perinatal period and to understand its potential clinical implications.</div></div><div><h3>Introduction</h3><div>Previous evidence associated ANS dysfunction and depressive symptomatology in the general population. Few observational and intervention studies investigated how HRV could be related to both pre- and post-partum depressive symptoms. However, high heterogeneity in the study designs and methods has been reported. Therefore, this scoping review plans to combine all these findings to build a starting point for future research.</div></div><div><h3>Inclusion criteria</h3><div>This scoping review will consider articles focusing on the association between HRV and depression in the peripartum and – when available – on the impact of interventions on HRV and how this correlates with changes in depressive symptoms. Studies will be included with no restrictions on participants’ age, peripartum time points for the assessment, and HRV parameters collected.</div></div><div><h3>Methods</h3><div>We will perform a systematic search using the Medline (PubMed), PsychInfo, and Web of Science (WoS) databases. Two authors will independently screen titles, abstracts, and then full-text articles that meet the inclusion criteria. The review will include only journal articles published in English, with no time limitations. Data will be extracted and presented in tables and/or graphical representations to summarise and describe the results. Extracted data will be reported in a comprehensive summary.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100885"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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