HIV-1 Infection and Central Monoamine Neurotransmitters

Abstract

Human immunodeficiency virus type 1 (HIV-1) enters the central nervous system (CNS) shortly after infection and gets localized in different brain regions, leading to various types of neuropathological problems. It has been hypothesized that HIV-1 infection mediated neuropathogenesis may also adversely affect the activity of the central monoamine neurotransmitters systems, such as dopamine (DA), and 5-hydroxytryptamine (5-HT, serotonin), resulting in neurocognitive deficits and mental health problems. However, investigations are scarce with respect to the status of these neurotransmitters in the CNS of HIV-1+ individuals, particularly in those patients who had received antiretroviral therapy (ART) during life. Since, mental health problems and neurocognitive and neuropsychological deficits continue to persist even after ART intervention, it is pertinent to determine the CNS status of the neurotransmitters associated with these functions. We determined the neurotransmitters, dopamine and its metabolite, homovanillic acid (HVA) in different brain regions of a group of autopsied cases of HIV-1+ and HIV-1 negative controls, using highly sensitive CoulArray HPLC-ECD system. Distribution of HIV-1 viral RNA in these brain regions was also measured using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) technology with high sensitivity of detection (<5 copies of RNA). In a separate study we reported measurement of 5-HT (serotonin) and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in the cerebrospinal fluid (CSF) obtained during life of neurologically asymptomatic HIV-1 infected patients and controls. A substantial decrease and a wide variation in the concentration of DA as well as its metabolite, homovanillic acid (HVA) was found in the autopsied brain regions of HIV-1 infected individuals. Wide variation was also found in HIV-1 RNA concentrations in different brain regions with no specific pattern observed in any region. Brain regions of HIV- negative individuals showed no detectable viral RNA. Majority of HIV-1+ individuals had demonstrated neurocognitive impairment during life despite ART intervention. A significant decrease in 5-HT concentration was also found in the CSF of HIV-1 infected patients. These studies demonstrate that HIV-1 infection adversely affects the central DA and 5-HT systems.