Mitochondrial injury and cognitive function in HIV infection and methamphetamine use.
Title | Mitochondrial injury and cognitive function in HIV infection and methamphetamine use. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Var, SR, Day, TRC, Vitomirov, A, Smith, DM, Soontornniyomkij, V, Moore, DJ, Achim, CL, Mehta, SR, Pérez-Santiago, J |
Journal | AIDS |
Volume | 30 |
Issue | 6 |
Pagination | 839-48 |
Date Published | 2016 Mar 27 |
ISSN | 1473-5571 |
Keywords | Adult, Brain, Central Nervous System Stimulants, Cognition, Cohort Studies, DNA, Mitochondrial, External, HIV Infections, Humans, Male, Methamphetamine, Middle Aged, Mitochondria, neurocognitive disorders, Polymerase Chain Reaction, Substance-Related Disorders |
Abstract | OBJECTIVE: In this work, we evaluated the association of human immunodeficiency virus (HIV) infection and methamphetamine (METH) use with mitochondrial injury in the brain and its implication on neurocognitive impairment.DESIGN: Mitochondria carry their genome (mtDNA) and play a critical role in cellular processes in the central nervous system. METH is commonly used in HIV-infected populations. HIV infection and METH use can cause damage to mtDNA and lead to neurocognitive morbidity. We evaluated HIV infection and METH use with mitochondrial injury in the brain.METHODS: We obtained white and gray matter from Brodmann areas 7, 8, 9, 46 of the following: HIV-infected individuals with history of past METH use (HIV+METH+, n = 16), HIV-infected individuals with no history of past METH use (HIV+METH-, n = 11), and HIV-negative controls (HIV-METH-, n = 30). We used the 'common deletion', a 4977 bp mutation, as a measurement of mitochondrial injury, and quantified levels of mtDNA and 'common deletion' by droplet digital PCR, and evaluated in relation to neurocognitive functioning [Global Deficit Score (GDS)].RESULTS: Levels of mtDNA and mitochondrial injury were highest in white matter of Brodmann area 46. A higher relative proportion of mtDNA carrying the 'common deletion' was associated with lower GDS (P < 0.01) in HIV+METH+ but higher GDS (P < 0.01) in HIV+METH-.CONCLUSIONS: Increased mitochondrial injury was associated with worse neurocognitive function in HIV+METH- individuals. Among HIV+METH+ individuals, an opposite effect was seen. |
DOI | 10.1097/QAD.0000000000001027 |
Alternate Journal | AIDS |
PubMed ID | 26807965 |
PubMed Central ID | PMC4785088 |
Grant List | R24-NS38841 / NS / NINDS NIH HHS / United States U24 MH100929 / MH / NIMH NIH HHS / United States U01 MH083507 / MH / NIMH NIH HHS / United States R01 MH105319 / MH / NIMH NIH HHS / United States R24 MH059724 / MH / NIMH NIH HHS / United States U01-MH083501 / MH / NIMH NIH HHS / United States K24 AI100665 / AI / NIAID NIH HHS / United States P50 DA026306 / DA / NIDA NIH HHS / United States R01 MH094159 / MH / NIMH NIH HHS / United States U24 MH100931 / MH / NIMH NIH HHS / United States P30 DA026306 / DA / NIDA NIH HHS / United States R01 AG043384 / AG / NIA NIH HHS / United States R24 NS045491 / NS / NINDS NIH HHS / United States U24 MH100928 / MH / NIMH NIH HHS / United States R25 MH081482 / MH / NIMH NIH HHS / United States R24-NS45491 / NS / NINDS NIH HHS / United States R24 MH059745 / MH / NIMH NIH HHS / United States R24 NS038841 / NS / NINDS NIH HHS / United States R24-MH59745 / MH / NIMH NIH HHS / United States K23 AI093163 / AI / NIAID NIH HHS / United States R01 MH096648 / MH / NIMH NIH HHS / United States R32-MH59724 / MH / NIMH NIH HHS / United States T32 AI007384 / AI / NIAID NIH HHS / United States DP1 DA034978 / DA / NIDA NIH HHS / United States U01 MH083501 / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States U01 MH083506 / MH / NIMH NIH HHS / United States U01-MH08021 / MH / NIMH NIH HHS / United States U01-MH083506 / MH / NIMH NIH HHS / United States P30 AI036214 / AI / NIAID NIH HHS / United States MH062512 / MH / NIMH NIH HHS / United States U24 MH100930 / MH / NIMH NIH HHS / United States R01 MH097520 / MH / NIMH NIH HHS / United States U01-MH083507 / MH / NIMH NIH HHS / United States U19 AI090970 / AI / NIAID NIH HHS / United States |