Abstract
Background: HIV-associated neurological disorder (HAND) has long been recognized as a consequence of human immunodeficiency virus (HIV) infection in the brain. The pathology of HAND gets more complicated with the recreational drug use such as cocaine. Recent studies have suggested multiple genetic influences involved in the pathology of addiction and HAND but only a fraction of the entire genetic risk has been investigated so far. In this regard, role of DJ1 protein (a gene linked to autosomal recessive early-onset Parkinson’s disease) in regulating dopamine (DA) transmission and reactive oxygen species (ROS) production in neuronal cells will be worth investigating in HIV-1 and cocaine exposed microenvironment. Being a very abundant protein in the brain, DJ1 could serve as a potential marker for early detection of HIV-1 and/or cocaine related neurological disorder.Methods: In vitro analysis was done to observe the effect of HIV-1 and/or cocaine on DJ1 protein expression in neuroblastoma cells (SK-N-MC). Gene and protein expression analysis of DJ1 was done on the HIV infected and/or cocaine treated SK-N-MC and compared to untreated cells using real time PCR, Western Blot and flow cytometry. Effect of DJ1 dysregulation on oxidative stress was analyzed by measuring ROS production in these cells.Results: Gene expression and protein analysis indicated that there was a significant decrease in DJ1 expression in SK-N-MC chronically exposed to HIV-1 and/or cocaine which is inversely proportional to ROS production.Conclusion: This is the first study to establish that DJ1 expression level in the neuronal cells significantly decreased in presence of HIV-1 and/or cocaine indicating oxidative stress level of DA neurons.
Highlights
The introduction of antiretroviral therapy (ART) has significantly improved the morbidity and mortality of human immunodeficiency virus (HIV) infected patients; the virus still persists in reservoirs like the brain even in ART treated patients (Best et al, 2009; Varatharajan and Thomas, 2009; Kanmogne et al, 2012)
The present study demonstrated an increase in HIV-1 replication (p24 level) in SK-N-MC up to 72 h which may have an effect in DJ1 down regulation along with cocaine which is subject to further investigation (Figure 3B)
HAART has reduced the frequency of HIV associated dementia (HAD) among HIV-infected patients, there are still different forms of neurological disorder that persist even in treated patients with cocaine abuse
Summary
The introduction of antiretroviral therapy (ART) has significantly improved the morbidity and mortality of human immunodeficiency virus (HIV) infected patients; the virus still persists in reservoirs like the brain even in ART treated patients (Best et al, 2009; Varatharajan and Thomas, 2009; Kanmogne et al, 2012). Several groups have reported increasing incidences of HIV related to cognitive impairment among virally suppressed HIV patients who are on ART for a longer period of time (Cysique et al, 2006; Tisch and Brew, 2009). This phenomenon poses an increasing challenge on identifying or treating HIV infected patients with neurological disorders. Being a very abundant protein in the brain, DJ1 could serve as a potential marker for early detection of HIV-1 and/or cocaine related neurological disorder
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