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.

The Selective Serotonin Reuptake Inhibitor Citalopram Decreases Human Immunodeficiency Virus Receptor and Coreceptor Expression in Immune Cells

“…In addition, recent studies have also demonstrated anti-inflammatory effects of SSRIs in microglia (63, 64). Relatedly, significant decreases in serotonin concentrations have been found in the CSF of HIV seropositive individuals (65). Thus, serotonin and SSRIs may regulate central and peripheral immune system function, potentially benefitting individuals with HIV (19, 20).…”

Selective impairments of alerting and executive control in HIV-infected patients: evidence from attention network test

“…It is demonstrated that the dopamine function plays a prominent role in executive attention network [ 18 ]. And, previous studies have reported that the cerebrospinal fluid dopamine mean values were significantly lower in HIV-infected subjects than HIV-seronegative group [ 35 , 36 ]. In addition, Kumar et al reported a strong correlation between specific HIV-1 viral load increases and dopamine reduction within the Substantia Nigra [ 37 ].…”

Screening Neuropharmacological Activities of <i>Kaempferia parviflora</i> (Krachai Dam) in Healthy Adult Male Rats

“…Previous studies had demonstrated that serotonin played a crucial role on various behavior including swimming behavior in forced swimming test (Detke et al, 1995) and learning and memory (Myhrer, 2003). It was found that serotonin contributed a crucial role on both acquisition and consolidation processes (Kumar et al, 2007). However, numerous neurotransmitters had been proposed to contribute the important role on learning and memory including acetylcholine (Zoladz and Diamond, 2008;Bustamam et al, 2008).…”