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Evidence for developmental dopaminergic alterations in the human immunodeficiency virus-1 transgenic rat
Katy M Webb1, Michael Y Aksenov, Charles F Mactutus
1Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine. katy.webb@uscmed.sc.edu
Insights
Human immunodeficiency virus (HIV) infection can cause neurologic issues in children, impacting their quality of life even with treatment. Research suggests the dopamine system in developing brains is uniquely vulnerable to HIV-1 infection.
Area of Science:
- Neuroscience
- Virology
- Pediatric Infectious Diseases
Background:
- Neurologic impairments in pediatric HIV patients can persist despite antiretroviral therapy (ART).
- Observed behavioral changes in HIV-infected children suggest alterations in dopaminergic neurotransmission.
Purpose of the Study:
- To investigate the impact of HIV-1 infection on the dopamine system in developing brains.
- To examine specific molecular changes in the dopaminergic pathway using a relevant animal model.
Main Methods:
- Utilized the HIV-1 transgenic rat model to study neurobiological effects.
- Analyzed protein expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT).
- Quantified messenger RNA (mRNA) levels for TH and DAT in the rat midbrain.
Main Results:
- Observed a significant increase in phosphorylated tyrosine hydroxylase protein expression.
- Found a decrease in dopamine transporter (DAT) mRNA levels.
- Noted no significant changes in overall tyrosine hydroxylase (TH) or dopamine transporter (DAT) protein levels or general gene/protein expression markers.
Conclusions:
- The dopamine system exhibits selective vulnerability in developing brains affected by HIV-1 infection.
- Specific molecular alterations, like increased phosphorylated TH and decreased DAT mRNA, indicate targeted neurobiological changes.
- These findings contribute to understanding the mechanisms behind neurologic impairments in pediatric HIV.
Abstract:
Neurologic impairments associated with human immunodeficiency virus (HIV) infection in pediatric patients may affect quality of life, and can develop despite antiretroviral therapy (ART). Behavioral changes observed in clinical studies of HIV-infected children suggest alterations in dopaminergic neurotransmission. Findings from our model of choice, the HIV-1 transgenic rat, reveal a significant increase in phosphorylated tyrosine hydroxylase protein expression and a decrease in dopamine transporter mRNA, without changes in tyrosine hydroxylase (TH) or dopamine transporter (DAT) protein or in more general markers of protein and gene expression levels in the HIV-1 transgenic rat midbrain. Thus these findings suggest selective vulnerability of the dopamine system in developing brains to HIV-1 infection.
