HIV-infection is associated with subcortical type of cognitive dysfunctions and motor disorders. Several lines of evidence suggest that central dopamine deficiency in humans plays an important role in the development of these dysfunctions. These observations have lead to the concept that central dopamine deficiency occurs in HIV-1 infection. Our earlier studies showing a decrease in the levels of dopamine in the cerebrospinal fluid (CSF) of HIV-1+ individuals support this concept. However, the relationship between central dopamine deficiency and cognitive dysfunctions in HIV-1 infection has not been fully investigated. The recent establishment of the NIH sponsored National NeuroAIDS Tissue Consortium (NNTC) has provided an opportunity to test the hypothesis that decreased dopamine levels in various areas of the brain will be related to the cognitive deficits in HIV-1 infection. This application proposes to test this hypothesis by quantifying levels of dopamine and its metabolite, homovanillic acid (HVA), in different areas of the brain of HIV-l+ cases with known cognitive status during life and in HIV-1- cases. It is proposed to investigate samples of brain and CSF obtained from a total of 60 adult men and women, age 19-50 (HIV-I+ cases, N=40; and HIV-1- cases, N=20), belonging to three ethnic groups (Caucasian, African-Americans, Hispanics). The brain tissue from HIV-1+ cases (N=40) will include 10each from those diagnosed with HAD, MCMD, NPI and no cognitive impairment. Tissue samples of the basal ganglia (caudate nucleus and putamen, globus pallidus), substantia nigra, and the frontal cortex, as well as CSF of obtained from the NNTC, and will be assayed for the levels of dopamine and its metabolite, HVA. It is hypothesized that the levels of dopamine and HVA will be decreased in the brain regions ofHIV-1+ cases with cognitive dysfunctions compared to that in HIV-1- cases. This application will also investigate the relationship between central viral load and dopamine/HVA levels, as well as explore the relationship of HAART intervention with dopamine/HVA levels in HIV-1+ individuals. These findings will be helpful in developing therapeutic strategies for interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS043982-02
Application #
6772442
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Nunn, Michael
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$215,888
Indirect Cost
Name
University of Miami School of Medicine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
052780918
City
Miami
State
FL
Country
United States
Zip Code
33146