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Current HIV Research


ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Research Article

Identification of the Differentially Expressed Genes Involved in the Synergistic Neurotoxicity of an HIV Protease Inhibitor and Methamphetamine

Author(s): Sangsang Li, Yanfei Li, Bingpeng Deng, Jie Yan* and Yong Wang*

Volume 17 , Issue 4 , 2019

Page: [290 - 303] Pages: 14

DOI: 10.2174/1570162X17666190924200354

Price: $65


Background: The abuse of psychostimulants such as methamphetamine (METH) is common in human immunodeficiency virus (HIV)-infected individuals. Acquired immunodeficiency syndrome (AIDS) patients taking METH and antiretroviral drugs could suffer severe neurologic damage and cognitive impairment.

Objective: To reveal the underlying neuropathologic mechanisms of an HIV protease inhibitor (PI) combined with METH, growth-inhibition tests of dopaminergic cells and RNA sequencing were performed.

Methods: A combination of METH and PI caused more growth inhibition of dopaminergic cells than METH alone or a PI alone. Furthermore, we identified differentially expressed gene (DEG) patterns in the METH vs. untreated cells (1161 genes), PI vs. untreated cells (16 genes), METH-PI vs. PI (3959 genes), and METH-PI vs. METH groups (14 genes).

Results: The DEGs in the METH-PI co-treatment group were verified in the brains of a mouse model using quantitative polymerase chain reaction and were involved mostly in the regulatory functions of cell proliferation and inflammation.

Conclusion: Such identification of key regulatory genes could facilitate the study of their neuroprotective potential in the users of METH and PIs.

Keywords: Methamphetamine, HIV protease inhibitor, synergistic neurotoxicity, RNA-seq, differentially expressed gene, AIDS.

Graphical Abstract
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