TY - JOUR
T1 - Combined Medication of Antiretroviral Drugs Tenofovir Disoproxil Fumarate, Emtricitabine, and Raltegravir Reduces Neural Progenitor Cell Proliferation In Vivo and In Vitro
AU - Xu, Peipei
AU - Wang, Yingchun
AU - Qin, Zhao
AU - Qiu, Lisha
AU - Zhang, Min
AU - Huang, Yunlong
AU - Zheng, Jialin C.
N1 - Funding Information:
Acknowledgements This work was supported by grants from National Key Basic Research Program of China (973 Program Grant No. 2014CB965000, project 1 No. 2014CB965001 and project 3 No. 2014CB965003), Innovative Research Groups of the National Natural Science Foundation of China (81221001 to JZ), Joint Research Fund for Overseas Chinese, Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China (81329002 to JZ), National Institutes of Health: 1R01NS097195-01 (JZ) and R03NS094071-01 (YH).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - FTC
KW - Neural progenitor cells
KW - RAL
KW - TDF
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U2 - 10.1007/s11481-017-9755-4
DO - 10.1007/s11481-017-9755-4
M3 - Article
C2 - 28735382
AN - SCOPUS:85025462758
VL - 12
SP - 682
EP - 692
JO - Journal of NeuroImmune Pharmacology
JF - Journal of NeuroImmune Pharmacology
SN - 1557-1890
IS - 4
ER -