Identification of the Differentially Expressed Genes Involved in the Synergistic Neurotoxicity of an HIV Protease Inhibitor and Methamphetamine.
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.
['Li|Sangsang|S|', 'Li|Yanfei|Y|', 'Deng|Bingpeng|B|', 'Yan|Jie|J|', 'Wang|Yong|Y|']
D000163:Acquired Immunodeficiency Syndrome D000818:Animals D045744:Cell Line, Tumor D000697:Central Nervous System Stimulants D019295:Computational Biology D004195:Disease Models, Animal D004357:Drug Synergism D020869:Gene Expression Profiling D005786:Gene Expression Regulation D063990:Gene Ontology D015658:HIV Infections D017320:HIV Protease Inhibitors D006801:Humans D008297:Male D008694:Methamphetamine D051379:Mice
differentially expressed gene HIV protease inhibitor Methamphetamine AIDS RNA-seq synergistic neurotoxicity.