Combined Medication of Antiretroviral Drugs Tenofovir Disoproxil Fumarate, Emtricitabine, and Raltegravir Reduces Neural Progenitor Cell Proliferation In Vivo and In Vitro

Peipei Xu, Yingchun Wang, Zhao Qin, Lisha Qiu, Min Zhang, Yunlong Huang, Jialin C. Zheng

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The application of combination antiretroviral therapy has greatly reduced the death rate from AIDS. However, up to 50% of patients on combination antiretroviral therapy develop HIV-associated neurocognitive disorders (HAND), which is associated with residual neuroinflammation and oxidative injury in the brain. Neural stem cells (NSCs) and progenitors play a vital role in repairing neuronal injuries. Therefore, we hypothesize that combination antiretroviral therapy may adversely affect NSCs/progenitors, contributing to the increasing prevalence of HAND. Here, we show that combined medication of three antiretroviral drugs tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and raltegravir (RAL) affects NSC homeostasis and progenitor proliferation in the mouse dentate gyrus (DG). Our results also show that TDF/FTC/RAL treatment prohibits proliferation and induces apoptosis of cultured mouse neural progenitor cells (NPCs), resulting in a reduction in the viability of NPCs. Moreover, we find that TDF, among the three drugs used in this combination antiretroviral treatment, accounts for most of the effects on neural progenitors. Together, our results offer a mechanistic explanation for the prevalence of HAND in AIDS patients treated with combination antiretroviral therapy.

Original languageEnglish (US)
Pages (from-to)682-692
Number of pages11
JournalJournal of Neuroimmune Pharmacology
Volume12
Issue number4
DOIs
StatePublished - Dec 1 2017

Keywords

  • FTC
  • Neural progenitor cells
  • RAL
  • TDF

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

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