期刊
CELLS
卷 10, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/cells10082158
关键词
dopamine; HIV-1; combination antiretroviral therapy; pre-pulse inhibition; attention; apathy; microglia; dendritic spines
类别
资金
- National Institutes of Health (NIH) [HD043680, MH106392, DA013137, NS100624]
This review critically examines the evidence for dopaminergic alterations following chronic exposure to HIV-1 viral proteins, concluding that long-term exposure leads to decreased dopamine function despite the use of combination antiretroviral therapy. It highlights the importance of focusing on strategies to rectify decreases in dopamine function for effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments.
Individuals living with human immunodeficiency virus type 1 (HIV-1) are often plagued by debilitating neurocognitive impairments and affective alterations;the pathophysiology underlying these deficits likely includes dopaminergic system dysfunction. The present review utilized four interrelated aims to critically examine the evidence for dopaminergic alterations following HIV-1 viral protein exposure. First, basal dopamine (DA) values are dependent upon both brain region andexperimental approach (i.e., high-performance liquid chromatography, microdialysis or fast-scan cyclic voltammetry). Second, neurochemical measurements overwhelmingly support decreased DA concentrations following chronic HIV-1 viral protein exposure. Neurocognitive impairments, including alterations in pre-attentive processes and attention, as well as apathetic behaviors, provide an additional line of evidence for dopaminergic deficits in HIV-1. Third, to date, there is no compelling evidence that combination antiretroviral therapy (cART), the primary treatment regimen for HIV-1 seropositive individuals, has any direct pharmacological action on the dopaminergic system. Fourth, the infection of microglia by HIV-1 viral proteins may mechanistically underlie the dopamine deficit observed following chronic HIV-1 viral protein exposure. An inclusive and critical evaluation of the literature, therefore, supports the fundamental conclusion that long-term HIV-1 viral protein exposure leads to a decreased dopaminergic state, which continues to persist despite the advent of cART. Thus, effective treatment of HIV-1-associated apathy/depression and neurocognitive impairments must focus on strategies for rectifying decreases in dopamine function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据