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Published on: September 19, 2010
Methamphetamine Increases the Proportion of SIV-Infected Microglia/Macrophages, Alters Metabolic Pathways, and
Meng Niu1, Brenda Morsey2, Benjamin G Lamberty2
1Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Abstract:
Both substance use disorder and HIV infection continue to affect many individuals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse, such as the psychostimulant methamphetamine. To determine the interaction of HIV and methamphetamine, we isolated microglia and brain macrophages from SIV-infected rhesus monkeys that were treated with or without methamphetamine. Cells were subjected to single-cell RNA sequencing and results were analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of the microglia and/or macrophages were infected by SIV. In addition, gene encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of microglia and/or macrophages from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.
Insights
Methamphetamine increases simian immunodeficiency virus (SIV) infection in the brain. This drug of abuse also negatively impacts brain cells, worsening the effects of HIV infection and substance use disorder.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Substance use disorder and HIV infection are prevalent global health issues.
- Both conditions adversely affect the brain and frequently co-occur.
- Microglia and macrophages in the brain are susceptible to HIV infection and affected by drugs like methamphetamine.
Purpose of the Study:
- To investigate the interaction between HIV (SIV in this model) and methamphetamine in the brain.
- To determine how methamphetamine affects SIV infection and brain cell responses.
Main Methods:
- Microglia and brain macrophages were isolated from SIV-infected rhesus monkeys.
- Animals were treated with or without methamphetamine.
- Single-cell RNA sequencing was performed, followed by statistical and bioinformatic analysis.
Main Results:
- Methamphetamine treatment significantly increased the proportion of SIV-infected microglia and macrophages.
- Gene expression indicated increased cell death pathways and inhibited brain-derived neurotrophic factor signaling.
- Distinct neuroinflammatory and metabolic pathway differences were observed in cells from methamphetamine-treated animals.
Conclusions:
- Methamphetamine exacerbates central nervous system (CNS) infection by SIV.
- The study highlights the combined detrimental effects of HIV infection and methamphetamine abuse on brain cells, including both infected and uninfected microglia and macrophages.
