Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults.

TitleLifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults.
Publication TypeJournal Article
Year of Publication2016
AuthorsSoontornniyomkij, V, Umlauf, A, Soontornniyomkij, B, Batki, IB, Moore, DJ, Masliah, E, Achim, CL
JournalJ Neurovirol
Date Published2016 10
KeywordsAdult, Aged, Alcoholism, Amphetamine-Related Disorders, Amyloid beta-Peptides, Autopsy, Calcium-Binding Proteins, DNA-Binding Proteins, Female, Frontal Lobe, Gene Expression, Glial Fibrillary Acidic Protein, Gliosis, HIV Infections, Humans, Internal, Male, Microfilament Proteins, Microtubule-Associated Proteins, Middle Aged, Opioid-Related Disorders, Parietal Lobe, Prosencephalon, Putamen, Synaptophysin, Temporal Lobe, White Matter

Methamphetamine (Meth) use is common among HIV-infected persons. It remains unclear whether Meth dependence is associated with long-lasting degenerative changes in the brain parenchyma and microvasculature of HIV-infected individuals. We examined the postmortem brains of 78 HIV-infected adults, twenty of whom were diagnosed with lifetime Meth dependence (18 past and two current at the final follow-up visit). Using logistic regression models, we analyzed associations of Meth with cerebral gliosis (immunohistochemistry for ionized calcium-binding adapter molecule-1 (Iba1) and glial fibrillary acidic protein (GFAP) in frontal, temporo-parietal, and putamen-internal capsule regions), synaptodendritic loss (confocal microscopy for synaptophysin (SYP) and microtubule-associated protein-2 (MAP2) in frontal cortex), β-amyloid plaque deposition (immunohistochemistry in frontal and temporo-parietal cortex and putamen), and arteriolosclerosis (histopathology in forebrain white matter). We found that Meth was associated with marked Iba1 gliosis in the temporo-parietal region (odds ratio, 4.42 (95 % confidence interval, 1.36, 14.39), p = 0.014, n = 62), which remained statistically significant after adjusting for HIV encephalitis, white matter lesions, and opportunistic diseases (n = 61); hepatitis C virus seropositivity (n = 54); and lifetime dependence on alcohol, opiates, and cannabis (n = 62). There was no significant association of Meth with GFAP gliosis, SYP or MAP2 loss, β-amyloid plaque deposition, or arteriolosclerosis. In conclusion, we found lifetime Meth dependence to be associated with focal cerebral microgliosis among HIV-infected adults, but not with other brain degenerative changes examined. Some of the changes in select brain regions might be reversible following extended Meth abstinence or, alternatively, might have not been induced by Meth initially.

Alternate JournalJ Neurovirol
PubMed ID27098516
PubMed Central IDPMC5055415
Grant ListU24 MH100929 / MH / NIMH NIH HHS / United States
U24 MH100925 / MH / NIMH 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
R01 AG043384 / AG / NIA NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R01 MH096648 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States