Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults.
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.
Department of Psychiatry, Translational Methamphetamine AIDS Research Center (TMARC), California NeuroAIDS Tissue Network (CNTN), School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA. vsoontor@ucsd.edu.
Virawudh
V
Soontornniyomkij
Department of Psychiatry, Translational Methamphetamine AIDS Research Center (TMARC), California NeuroAIDS Tissue Network (CNTN), School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA.
Anya
A
Umlauf
Department of Psychiatry, Translational Methamphetamine AIDS Research Center (TMARC), California NeuroAIDS Tissue Network (CNTN), School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA.
Benchawanna
B
Soontornniyomkij
Department of Psychiatry, Translational Methamphetamine AIDS Research Center (TMARC), California NeuroAIDS Tissue Network (CNTN), School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA.
Isabella B
IB
Batki
Department of Psychiatry, Translational Methamphetamine AIDS Research Center (TMARC), California NeuroAIDS Tissue Network (CNTN), School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA.
David J
DJ
Moore
Department of Pathology, California NeuroAIDS Tissue Network (CNTN), School of Medicine, University of California San Diego, La Jolla, CA, USA.|Department of Neurosciences, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Eliezer
E
Masliah
Department of Psychiatry, Translational Methamphetamine AIDS Research Center (TMARC), California NeuroAIDS Tissue Network (CNTN), School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA.
Cristian L
CL
Achim
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D019969:Amphetamine-Related Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D001344:Autopsy; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D015658:HIV Infections / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011699:Putamen / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D066127:White Matter / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
C112986:AIF1 protein, human; D016229:Amyloid beta-Peptides; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; C489788:MAP2 protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C569014:SYP protein, human; D016708:Synaptophysin
Arteriolosclerosis; Astrogliosis; Methamphetamine; Microgliosis; Small vessel disease; β-Amyloid