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| Publication Abstract Display | | Type: Published Abstract | | Title: Brain immunophilin response in HIV infected METH users. | | Authors: Achim CL, Soontornniyomkij V, Kaul M, Tatro E, Moore DJ, Everall IP, Grant I, Masliah E | | Year: 2009 | | Publication: Journal of NeuroVirology | | Volume: 15 Issue: S1 Pages: 2 | | Abstract:Background. Chronic stress is associated with disruption of the glucocorticoid receptor (GR) homeostasis in the brain. Signaling through the GR requires its translocation to the nucleus. A key molecule in this process is the immunophilin FKBP52. Our previous studies have established that increased expression of brain immunophilins (IP) is a good indicator of neuronal stress in HIV infection. We hypothesize that methamphetamine (METH) use, a common comorbid factor in HIV infected patients, will further amplify the IP response in the brain.
Materials and Methods. To test our hypothesis we have initiated a retrospective autopsy study of IP and GR expression in the brain of HIV/METH users compared to HIV non-METH subjects. For in vivo studies we are using transgenic animals expressing HIV gp120 in the brain (gp120 TG) exposed to a METH binge regimen. The distribution of brain IP and GR are measured by quantitative immunohistochemistry.
Results. Our preliminary autopsy studies show that in the HIV/METH human brains the expression in the subcortical white matter (WM) of both FKBP52 and GR is significantly increased when compared to the HIV non-METH subjects. In the in vivo mouse model, the gp120 TG animals exposed to METH show impaired learning in the water maze testing, when compared to littermate controls. The necropsy studies show again increased GR and FKBP52 immunoreactivity in the frontal cortex.
Discussion. Increased FKBP52 expression in the WM of METH users is consistent with our previous finding of IP reactivity in degenerating axons. The preliminary analysis of increased GR reactivity in the WM indicates glial activation. Our results suggest a WM-associated substrate for the neuronal stress in HIV infected METH users, which in turn may be related to chronic neuroinflammation.
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HIV disease and neurologic complications --- NeuroAIDS and minor neurocognitive disorders --- Substance abuse and other co-morbidities. |
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