Effect of buprenorphine on monocytes in the context of neuroAids and opioid abuse

神经辅助药物和阿片类药物滥用中丁丙诺啡对单核细胞的影响

基本信息

项目摘要

The HIV and opioid epidemics intersect, impacting millions of people worldwide. Antiretroviral therapy (ART) has improved and extended the lives of people with HIV, PWH. However, milder chronic HIV associated neurocognitive impairments known as mild HAND or HIV-NCI persist. HIV-NCI affect 15-40% of PWH and because they persist for life, worsen with age, and affect adherence to medications, they can significantly reduce quality of life and increase mortality risk. Many PWH have opioid use disorder, OUD, a comorbidity in PWH that can exacerbate HIV-NCI. Our novel findings in the first funding cycle demonstrate that buprenorphine, a well-established opioid agonist therapy used to treat OUD, may also be a therapy for NCI. Buprenorphine acts as a partial agonist to the mu opioid receptor (MOR) and full antagonist to the kappa opioid receptor (KOR) and according to some studies, it may improve neuropsychological outcomes in people with OUD with or without chronic HIV infection. Our studies suggest that this beneficial activity of buprenorphine may due to its interactions with peripheral blood CD14+CD16+ monocytes, which we showed express MOR and KOR, are preferentially infected with HIV, and have a selective advantage to cross the blood brain barrier (BBB) in response to CCL2 in vitro. This increased transmigration is reduced by buprenorphine, in part by its ability to limit CCL2/CCR2 signaling. Our novel findings in EcoHIV infected mice with HIV-NCI demonstrate that buprenorphine treatment can reverse HIV-NCI in these mice in correlation with a decrease in inflammatory monocytes in their brains, reduction in HIV brain burden, and a reduction in dendritic pruning, a marker of HIV mediated NCI. We hypothesize that buprenorphine mitigates HIV neuropathogenesis and can treat HIV-NCI in PWH with and without OUD. We also propose that this is mediated through its activity on the Mu and Kappa opioid receptors. Our studies will also identify receptor(s) by which buprenorphine is exerting its mechanism of action and will enable the development of second-generation therapies derived from buprenorphine that specifically target these receptor(s). In Aim1, we will characterize in vitro mechanisms of buprenorphine mediated inhibition of CD14+CD16+ monocyte transmigration across the BBB and characterize the role of MOR and KOR in these processes. In Aim 2, we will use genetically modified mice to address individual and combined roles of MOR and KOR in buprenorphine therapy in the preclinical model of EcoHIV driven HIV-NCI and the importance of these receptors specifically on myeloid cells in NCI development. In Aim 3, we will characterize transmigration across a BBB model of mature human monocytes using PBMC from PWH on buprenorphine and correlate this with the PWH's cognitive functions. These will provide further support for use of buprenorphine as a therapy for HIV-NCI in PWH with and without OUD. The studies will be performed by a highly interactive group of HIV scientists, animal model specialists, and infectious diseases, HIV, and OUD physician scientists, and a neuropscychologist, all recognized experts in CNS disease.
艾滋病毒和阿片类药物流行病相互交织,影响着全世界数百万人。抗逆转录病毒治疗(ART)

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Joan Weinberger Berman其他文献

Joan Weinberger Berman的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Joan Weinberger Berman', 18)}}的其他基金

The impact of methamphetamine on CXCL12 mediated HIV neuropathogenesis
甲基苯丙胺对 CXCL12 介导的 HIV 神经发病机制的影响
  • 批准号:
    10547875
  • 财政年份:
    2022
  • 资助金额:
    $ 78.57万
  • 项目类别:
Inflammation, BBB disruption, and Reward Function in the Pathogenesis of Depression among PWH
感染者抑郁症发病机制中的炎症、血脑屏障破坏和奖赏功能
  • 批准号:
    10535898
  • 财政年份:
    2022
  • 资助金额:
    $ 78.57万
  • 项目类别:
The impact of methamphetamine on CXCL12 mediated HIV neuropathogenesis
甲基苯丙胺对 CXCL12 介导的 HIV 神经发病机制的影响
  • 批准号:
    10666675
  • 财政年份:
    2022
  • 资助金额:
    $ 78.57万
  • 项目类别:
Inflammation, BBB disruption, and Reward Function in the Pathogenesis of Depression among PWH
感染者抑郁症发病机制中的炎症、血脑屏障破坏和奖赏功能
  • 批准号:
    10707230
  • 财政年份:
    2022
  • 资助金额:
    $ 78.57万
  • 项目类别:
Mechanisms of opioid- mediated HIV neuropathogenesis
阿片类药物介导的 HIV 神经发病机制
  • 批准号:
    10383747
  • 财政年份:
    2019
  • 资助金额:
    $ 78.57万
  • 项目类别:
Mechanisms of opioid- mediated HIV neuropathogenesis
阿片类药物介导的 HIV 神经发病机制
  • 批准号:
    9767913
  • 财政年份:
    2019
  • 资助金额:
    $ 78.57万
  • 项目类别:
Mechanisms of opioid- mediated HIV neuropathogenesis
阿片类药物介导的 HIV 神经发病机制
  • 批准号:
    9919529
  • 财政年份:
    2019
  • 资助金额:
    $ 78.57万
  • 项目类别:
Mechanisms of opioid- mediated HIV neuropathogenesis
阿片类药物介导的 HIV 神经发病机制
  • 批准号:
    10612386
  • 财政年份:
    2019
  • 资助金额:
    $ 78.57万
  • 项目类别:
Monocyte CNS HIV entry & neurodegeneration: Translational studies in the CART era
单核细胞 CNS HIV 进入
  • 批准号:
    9915978
  • 财政年份:
    2017
  • 资助金额:
    $ 78.57万
  • 项目类别:
Monocyte CNS HIV entry & neurodegeneration: Translational studies in the CART era
单核细胞 CNS HIV 进入
  • 批准号:
    9407532
  • 财政年份:
    2017
  • 资助金额:
    $ 78.57万
  • 项目类别:

相似海外基金

Pharmacy-led Transitions of Care Intervention to Address System-Level Barriers and Improve Medication Adherence in Socioeconomically Disadvantaged Populations
药房主导的护理干预转型,以解决系统层面的障碍并提高社会经济弱势群体的药物依从性
  • 批准号:
    10594350
  • 财政年份:
    2023
  • 资助金额:
    $ 78.57万
  • 项目类别:
Evaluating Centralizing Interventions to Address Low Adherence to Lung Cancer Screening Follow-up in Decentralized Settings
评估集中干预措施,以解决分散环境中肺癌筛查随访依从性低的问题
  • 批准号:
    10738120
  • 财政年份:
    2023
  • 资助金额:
    $ 78.57万
  • 项目类别:
Suubi-Mhealth: A mobile health intervention to address depression and improve ART adherence among Youth living with HIV (YLHIV) in Uganda
Suubi-Mhealth:一种移动健康干预措施,旨在解决乌干达艾滋病毒感染者 (YLHIV) 青少年的抑郁症问题并提高抗逆转录病毒疗法的依从性
  • 批准号:
    10526768
  • 财政年份:
    2022
  • 资助金额:
    $ 78.57万
  • 项目类别:
Suubi-Mhealth: A mobile health intervention to address depression and improve ART adherence among Youth living with HIV (YLHIV) in Uganda
Suubi-Mhealth:一种移动健康干预措施,旨在解决乌干达艾滋病毒感染者 (YLHIV) 青少年的抑郁症问题并提高抗逆转录病毒疗法的依从性
  • 批准号:
    10701072
  • 财政年份:
    2022
  • 资助金额:
    $ 78.57万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10679092
  • 财政年份:
    2021
  • 资助金额:
    $ 78.57万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10432133
  • 财政年份:
    2021
  • 资助金额:
    $ 78.57万
  • 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
  • 批准号:
    10327065
  • 财政年份:
    2021
  • 资助金额:
    $ 78.57万
  • 项目类别:
Leveraging Technology to Address Access and Adherence to Conventional Hospital-Based Pulmonary Rehabilitation in Veterans with COPD
利用技术解决慢性阻塞性肺病退伍军人接受和坚持传统医院肺康复的问题
  • 批准号:
    10377366
  • 财政年份:
    2019
  • 资助金额:
    $ 78.57万
  • 项目类别:
Leveraging Technology to Address Access and Adherence to Conventional Hospital-Based Pulmonary Rehabilitation in Veterans with COPD
利用技术解决慢性阻塞性肺病退伍军人接受和坚持传统医院肺康复的问题
  • 批准号:
    10574496
  • 财政年份:
    2019
  • 资助金额:
    $ 78.57万
  • 项目类别:
Targeted interventions to address the multi-level effects of gender-based violence on PrEP uptake and adherence among adolescent girls and young women in Kenya
有针对性的干预措施,以解决性别暴力对肯尼亚少女和年轻妇女接受和坚持 PrEP 的多层面影响
  • 批准号:
    9403567
  • 财政年份:
    2017
  • 资助金额:
    $ 78.57万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了