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Published on: September 19, 2010
Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults
Virawudh Soontornniyomkij1, Anya Umlauf2, Benchawanna Soontornniyomkij2
1Department 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.
Abstract:
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.
Insights
Methamphetamine dependence in HIV-infected individuals is linked to specific brain changes, particularly focal microgliosis in the temporo-parietal region. Other degenerative changes were not significantly associated with methamphetamine use.
Area of Science:
- Neuroscience
- Infectious Diseases
- Toxicology
Background:
- Methamphetamine (Meth) use is prevalent among individuals with HIV.
- The long-term neurological consequences of Meth dependence in HIV-infected populations are not fully understood.
- Investigating brain changes associated with Meth use in HIV is crucial for understanding disease progression and potential interventions.
Purpose of the Study:
- To determine if Meth dependence is associated with lasting degenerative changes in the brain parenchyma and microvasculature of HIV-infected adults.
- To analyze the association between lifetime Meth dependence and specific neuropathological markers, including gliosis, synaptodendritic loss, amyloid deposition, and arteriolosclerosis.
Main Methods:
- Postmortem brain tissue analysis from 78 HIV-infected adults (20 with lifetime Meth dependence).
- Utilized immunohistochemistry and confocal microscopy to assess cerebral gliosis (Iba1, GFAP), synaptodendritic loss (SYP, MAP2), and β-amyloid plaque deposition.
- Histopathology was used to evaluate arteriolosclerosis; logistic regression models analyzed associations, adjusting for confounding factors.
Main Results:
- Methamphetamine dependence was significantly associated with marked ionized calcium-binding adapter molecule-1 (Iba1) gliosis in the temporo-parietal region (OR, 4.42; p=0.014).
- This association remained significant after adjusting for HIV encephalitis, white matter lesions, opportunistic diseases, hepatitis C virus seropositivity, and substance dependence (alcohol, opiates, cannabis).
- No significant associations were found between Meth dependence and glial fibrillary acidic protein (GFAP) gliosis, synaptodendritic loss, β-amyloid plaque deposition, or arteriolosclerosis.
Conclusions:
- Lifetime Meth dependence is associated with focal cerebral microgliosis in HIV-infected adults.
- The study did not find associations between Meth dependence and other examined degenerative brain changes.
- Potential reversibility of observed changes with abstinence or alternative initial causes warrants further investigation.
