NeuroImmune pharmacology and therapeutics最新文献_第5页

Quantifying the Neuropsychiatric Symptoms in Post-Acute Sequelae of COVID-19 (PASC) using the NIH Toolbox^® and PROMIS. 使用NIH工具箱®和PROMIS量化COVID-19急性后后遗症（PASC）的神经精神症状

NeuroImmune pharmacology and therapeutics Pub Date : 2023-06-20 Epub Date: 2022-08-15 DOI: 10.1515/nipt-2022-0010

Meghann C Ryan, Huajun Liang, Eleanor Wilson, Andrea Levine, Shyamasundaran Kottilil, Thomas Ernst, Linda Chang

{"title":"Quantifying the Neuropsychiatric Symptoms in Post-Acute Sequelae of COVID-19 (PASC) using the NIH Toolbox® and PROMIS.","authors":"Meghann C Ryan, Huajun Liang, Eleanor Wilson, Andrea Levine, Shyamasundaran Kottilil, Thomas Ernst, Linda Chang","doi":"10.1515/nipt-2022-0010","DOIUrl":"10.1515/nipt-2022-0010","url":null,"abstract":"Objective: To quantify neuropsychiatric symptoms reported by individuals with Post-Acute Sequelae of COVID-19 (PASC) using the NIH Toolbox® for Assessment of Neurological and Behavioral Function (NIHTB) and Patient-Reported Outcomes Measurement Information System (PROMIS).Methods: 30 PASC (20 women, 21-63 years) and 27 control (16 women, 25-68 years) participants completed three NIHTB batteries and selected PROMIS tests. Group differences on fully corrected T-scores were evaluated using analysis of covariance and Cohen's d effect sizes. A linear regression model predicted the effects from time since diagnosis.Results: PASC had poorer emotional health and motor function than controls, including poorer locomotion, endurance and dexterity, but normal cognitive function, ~7 months post-infection, compared to controls. PASC participants had a steeper age-related decline on 2-Minute Walk than controls. T-scores on four cognitive and three motor tests improved with longer time since diagnosis.Conclusion: NIHTB and PROMIS captured the poorer emotional health and motor function in PASC, including the novel findings of deficits locomotion and dexterity. The normal cognitive performance suggests subclinical effects that may be compensated by neural and cognitive reserves, and manifested subjectively by the negative psychological effects and fatigue. The persistent emotional and psychiatric symptoms necessitate mental health treatment be prioritized.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 2","pages":"95-101"},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373798/pdf/nihms-1872875.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260959","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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The 27th Scientific Conference of the Society on NeuroImmune Pharmacology: New Delhi, India, March 15-18, 2023. 神经免疫药理学学会第27届科学会议:印度新德里，2023年3月15-18日。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-06-01 DOI: 10.1515/nipt-2023-0006

Sulie L Chang, Pankaj Seth, Jun Zhu, Gurudutt Pendyala, Jean M Bidlack, Santosh Kumar

引用次数: 0

Constitutive expression of HIV-1 viral proteins induces progressive synaptodendritic alterations in medium spiny neurons: implications for substance use disorders HIV-1病毒蛋白的组成型表达诱导中棘神经元进行性突触树突改变：与物质使用障碍的关系

NeuroImmune pharmacology and therapeutics Pub Date : 2023-06-01 DOI: 10.1515/nipt-2023-0008

K. McLaurin, Hailong Li, C. Mactutus, R. Booze

{"title":"Constitutive expression of HIV-1 viral proteins induces progressive synaptodendritic alterations in medium spiny neurons: implications for substance use disorders","authors":"K. McLaurin, Hailong Li, C. Mactutus, R. Booze","doi":"10.1515/nipt-2023-0008","DOIUrl":"https://doi.org/10.1515/nipt-2023-0008","url":null,"abstract":"Abstract Objectives Perinatally-infected adolescents living with HIV-1 (pALHIV) appear uniquely vulnerable to developing substance use disorders (SUD). Medium spiny neurons (MSNs) in the nucleus accumbens core (NAcc), an integrator of cortical and thalamic input, have been implicated as a key structural locus for the pathogenesis of SUD. To date, however, how constitutive expression of HIV-1 viral proteins alters the development of MSNs in the NAcc has not been systematically evaluated. Methods An innovative ballistic labeling technique was utilized to examine MSNs in the NAcc, and associated dendritic spines, in HIV-1 transgenic (Tg) and control animals. First, a time-sequential longitudinal experimental design was implemented, whereby animals were sacrificed at 30-day intervals from postnatal day (PD) 30 to PD 180. Second, the therapeutic efficacy of S-Equol for HIV-1-associated synaptic dysfunction in MSNs was evaluated using a cross-sectional experimental design. Results Constitutive expression of HIV-1 viral proteins disrupted the development of MSNs, evidenced by alterations in neuritogenesis and synaptogenesis. Furthermore, age-related, progressive synaptodendritic alterations were observed in the patterning of dendritic branches and dendritic spines, as well as dendritic spine head diameter, in HIV-1 Tg, relative to control, animals. Treatment with S-Equol during the formative period, however, led to long-term enhancements in synaptic function (i.e., PD 180). Conclusions Developmental and progressive synaptodendritic alterations in MSNs induced by chronic HIV-1 viral protein exposure may underlie the increased propensity for pALHIV to develop SUD. Elucidating a potential neural mechanism underlying the unique vulnerability of pALHIV to SUD affords a fundamental opportunity for the evaluation of therapeutics.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"153 - 167"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49631413","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}

引用次数: 1

Frontmatter 头版头条

NeuroImmune pharmacology and therapeutics Pub Date : 2023-06-01 DOI: 10.1515/nipt-2023-frontmatter2

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HIV Tat-mediated altered oligodendrocyte maturation involves autophagy-lysosomal dysfunction HIV Tat介导的少突胶质细胞成熟改变涉及自噬溶酶体功能障碍

NeuroImmune pharmacology and therapeutics Pub Date : 2023-06-01 DOI: 10.1515/nipt-2023-0007

Alpika Tripathi, P. Periyasamy, M. Guo, S. Buch

{"title":"HIV Tat-mediated altered oligodendrocyte maturation involves autophagy-lysosomal dysfunction","authors":"Alpika Tripathi, P. Periyasamy, M. Guo, S. Buch","doi":"10.1515/nipt-2023-0007","DOIUrl":"https://doi.org/10.1515/nipt-2023-0007","url":null,"abstract":"Abstract Objectives The current study was undertaken to understand the underlying molecular mechanism(s) by which HIV Transactivator of transcription (Tat) alters oligodendrocyte maturation through the generation of reactive oxygen species (ROS), impairment of lysosomal functioning, and dysregulation of autophagy. Methods We exposed primary rat immature oligodendrocytes to HIV Tat and utilized various experimental techniques to assess its effects on oligodendrocytes maturation. We measured ROS levels, assessed lysosomal membrane potential, determined cathepsin D activity, and analyzed the expression of autophagy-related markers. Furthermore, we investigated the potential of ROS scavengers and lysosomal protectants to mitigate the damaging effects of HIV Tat on oligodendrocytes maturation. Results Exposure of primary rat immature oligodendrocytes to HIV Tat significantly increased ROS levels, indicating the induction of oxidative stress. This oxidative stress impaired lysosomal functioning, as evidenced by a substantial increase in lysosomal membrane potential and a decrease in cathepsin D activity. Compromised lysosomal function resulted in dysregulated autophagy, which was confirmed by increased expression of SQSTM1. However, the administration of ROS scavengers and lysosomal protectants effectively attenuated the detrimental effects of HIV Tat on oligodendrocytes maturation. Conclusions Our findings demonstrate that HIV Tat exposure induces oxidative stress, impairs lysosomal functioning, and dysregulates autophagy in oligodendrocytes. These molecular changes likely contribute to the altered maturation of oligodendrocytes observed in HIV-infected individuals. Understanding these underlying mechanisms provides valuable insights into the pathogenesis of HIV-associated neurocognitive disorders and highlights the potential of therapeutic strategies targeting ROS scavenging and lysosomal protection as adjunctive approaches for managing such complications in HIV +ve individuals.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"139 - 151"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46930059","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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Early-career research education mentoring: a successful program in NeuroHIV and mental health (TRNAMH) 早期职业研究教育指导：神经HIV和心理健康（TRNAMH）的一个成功项目

NeuroImmune pharmacology and therapeutics Pub Date : 2023-05-08 DOI: 10.1515/nipt-2023-0009

H. Thomas, Asante R. Kamkwalala, A. Nath, J. Mcarthur, V. Wojna, B. Shiramizu, N. Sacktor, C. Pardo, N. Haughey, Janice Clements, J. Mankowski, Christine Zink, Joseph Steiner, M. Pomper, Linda Chang, B. Ances, Kurt Hauser, S. Letendre, M. Stins, V. Nerurkar, S. Buch, T. Burdo, L. Rubin, Takashi Tsukamoto, M. Pletnikov, R. Salas, C. Gamaldo, Peter H. Dziedzic, Amanda M. Brown

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The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART. 慢性可卡因使用、B细胞紊乱和艾滋病病毒感染者接受抑制性抗逆转录病毒治疗后免疫恢复迟钝之间的联系

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2023-03-27 DOI: 10.1515/nipt-2022-0019

Da Cheng, Zhenwu Luo, Sylvia Fitting, William Stoops, Sonya L Heath, Lishomwa C Ndhlovu, Wei Jiang

{"title":"The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART.","authors":"Da Cheng, Zhenwu Luo, Sylvia Fitting, William Stoops, Sonya L Heath, Lishomwa C Ndhlovu, Wei Jiang","doi":"10.1515/nipt-2022-0019","DOIUrl":"10.1515/nipt-2022-0019","url":null,"abstract":"Background: We recently reveal that anti-CD4 autoantibodies contribute to blunted CD4+ T cell reconstitution in HIV+ individuals on antiretroviral therapy (ART). Cocaine use is common among HIV+ individuals and is associated with accelerated disease progression. However, the mechanisms underlying cocaine-induced immune perturbations remain obscure.Methods: We evaluated plasma levels of anti-CD4 IgG and markers of microbial translocation, as well as B-cell gene expression profiles and activation in HIV+ chronic cocaine users and non-users on suppressive ART, as well as uninfected controls. Plasma purified anti-CD4 IgGs were assessed for antibody-dependent cytotoxicity (ADCC).Results: HIV+ cocaine users had increased plasma levels of anti-CD4 IgGs, lipopolysaccharide (LPS), and soluble CD14 (sCD14) versus non-users. An inverse correlation was observed in cocaine users, but not non-drug users. Anti-CD4 IgGs from HIV+ cocaine users mediated CD4+ T cell death through ADCC in vitro. B cells from HIV+ cocaine users exhibited activation signaling pathways and activation (cycling and TLR4 expression) related to microbial translocation versus non-users.Conclusions: This study improves our understanding of cocaine associated B cell perturbations and immune failure and the new appreciation for autoreactive B cells as novel therapeutic targets.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"71-79"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9563743","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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Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19. COVID-19 后出现持续神经精神症状的参与者大脑弥散异常。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2023-01-05 DOI: 10.1515/nipt-2022-0016

Huajun Liang, Thomas Ernst, Kenichi Oishi, Meghann C Ryan, Edward Herskovits, Eric Cunningham, Eleanor Wilson, Shyamasundaran Kottilil, Linda Chang

{"title":"Abnormal brain diffusivity in participants with persistent neuropsychiatric symptoms after COVID-19.","authors":"Huajun Liang, Thomas Ernst, Kenichi Oishi, Meghann C Ryan, Edward Herskovits, Eric Cunningham, Eleanor Wilson, Shyamasundaran Kottilil, Linda Chang","doi":"10.1515/nipt-2022-0016","DOIUrl":"10.1515/nipt-2022-0016","url":null,"abstract":"Objectives: We aimed to compare brain white matter integrity in participants with post-COVID-19 conditions (PCC) and healthy controls.Methods: We compared cognitive performance (NIH Toolbox®), psychiatric symptoms and diffusion tensor imaging (DTI) metrics between 23 PCC participants and 24 controls. Fractional anisotropy (FA), axial (AD), radial (RD), and mean (MD) diffusivities were measured in 9 white matter tracts and 6 subcortical regions using MRICloud.Results: Compared to controls, PCC had similar cognitive performance, but greater psychiatric symptoms and perceived stress, as well as higher FA and lower diffusivities in multiple white matter tracts (ANCOVA-p-values≤0.001-0.048). Amongst women, PCC had higher left amygdala-MD than controls (sex-by-PCC p=0.006). Regardless of COVID-19 history, higher sagittal strata-FA predicted greater fatigue (r=0.48-0.52, p<0.001) in all participants, and higher left amygdala-MD predicted greater fatigue (r=0.61, p<0.001) and anxiety (r=0.69, p<0.001) in women, and higher perceived stress (r=0.45, p=0.002) for all participants.Conclusions: Microstructural abnormalities are evident in PCC participants averaged six months after COVID-19. The restricted diffusivity (with reduced MD) and higher FA suggest enhanced myelination or increased magnetic susceptibility from iron deposition, as seen in stress conditions. The higher amygdala-MD in female PCC suggests persistent neuroinflammation, which might contribute to their fatigue, anxiety, and perceived stress.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"37-48"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9318993","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}

引用次数: 0

Dual-Peak Lorentzian CEST MRI for antiretroviral drug brain distribution. 抗逆转录病毒药物脑分布的双峰洛伦兹CEST磁共振成像。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2022-09-13 DOI: 10.1515/nipt-2022-0012

Yutong Liu, Gabriel C Gauthier, Howard E Gendelman, Aditya N Bade

{"title":"Dual-Peak Lorentzian CEST MRI for antiretroviral drug brain distribution.","authors":"Yutong Liu, Gabriel C Gauthier, Howard E Gendelman, Aditya N Bade","doi":"10.1515/nipt-2022-0012","DOIUrl":"10.1515/nipt-2022-0012","url":null,"abstract":"Objectives: Spatial-temporal biodistribution of antiretroviral drugs (ARVs) can now be achieved using MRI by utilizing chemical exchange saturation transfer (CEST) contrasts. However, the presence of biomolecules in tissue limits the specificity of current CEST methods. To overcome this limitation, a Lorentzian line-shape fitting algorithm was developed that simultaneously fits CEST peaks of ARV protons on its Z-spectrum.Case presentation: This algorithm was tested on the common first line ARV, lamivudine (3TC), that has two peaks resulting from amino (-NH2) and hydroxyl (-OH) protons in 3TC. The developed dual-peak Lorentzian function fitted these two peaks simultaneously, and used the ratio of -NH2 and -OH CEST contrasts as a constraint parameter to measure 3TC presence in brains of drug-treated mice. 3TC biodistribution calculated using the new algorithm was compared against actual drug levels measured using UPLC-MS/MS. In comparison to the method that employs the -NH2 CEST peak only, the dual-peak Lorentzian fitting algorithm showed stronger correlation with brain tissue 3TC levels, signifying estimation of actual drug levels.Conclusions: We concluded that 3TC levels can be extracted from confounding CEST effects of tissue biomolecules resulting in improved specificity for drug mapping. This algorithm can be expanded to measure a variety of ARVs using CEST MRI.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"63-69"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9270378","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}

引用次数: 0

The impact of cannabinoids on inflammasome signaling in HIV-1 infection. 大麻素对 HIV-1 感染中炎性信号转导的影响。

NeuroImmune pharmacology and therapeutics Pub Date : 2023-03-25 Epub Date: 2023-02-23 DOI: 10.1515/nipt-2023-0002

Alice K Min, Aislinn M Keane, Matthew Paltiel Weinstein, Talia H Swartz

{"title":"The impact of cannabinoids on inflammasome signaling in HIV-1 infection.","authors":"Alice K Min, Aislinn M Keane, Matthew Paltiel Weinstein, Talia H Swartz","doi":"10.1515/nipt-2023-0002","DOIUrl":"10.1515/nipt-2023-0002","url":null,"abstract":"Human immunodeficiency virus type 1 (HIV-1) is a chronic disease that afflicts over 38 million people worldwide without a known cure. The advent of effective antiretroviral therapies (ART) has significantly decreased the morbidity and mortality associated with HIV-1 infection in people living with HIV-1 (PWH), thanks to durable virologic suppression. Despite this, people with HIV-1 experience chronic inflammation associated with co-morbidities. While no single known mechanism accounts for chronic inflammation, there is significant evidence to support the role of the NLRP3 inflammasome as a key driver. Numerous studies have demonstrated therapeutic impact of cannabinoids, including exerting modulatory effects on the NLRP3 inflammasome. Given the high rates of cannabinoid use in PWH, it is of great interest to understand the intersecting biology of the role of cannabinoids in HIV-1-associated inflammasome signaling. Here we describe the literature of chronic inflammation in people with HIV, the therapeutic impact of cannabinoids in PWH, endocannabinoids in inflammation, and HIV-1-associated inflammation. We describe a key interaction between cannabinoids, the NLRP3 inflammasome, and HIV-1 viral infection, which supports further investigation of the critical role of cannabinoids in HIV-1 infection and inflammasome signaling.","PeriodicalId":74278,"journal":{"name":"NeuroImmune pharmacology and therapeutics","volume":"2 1","pages":"79-88"},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264692","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}

引用次数: 0