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

Abstract

BACKGROUND\nThe 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.\n\n\nOBJECTIVE\nTo reveal the underlying neuropathologic mechanisms of a HIV protease inhibitor (PI) combined with METH, growth-inhibition tests of dopaminergic cells and RNA sequencing were performed.\n\n\nMETHODS\nA combination of METH and a 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).\n\n\nRESULTS\nThe 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.\n\n\nCONCLUSION\nSuch identification of key regulatory genes could facilitate study of their neuroprotective potential in the users of METH and PIs.