Patterns of selective neuronal damage in methamphetamine-user AIDS patients.
The risk for HIV infection attributable to methamphetamine (METH) use continues to increase. The combined effect of HIV and METH in the pathogenesis of HIV encephalitis (HIVE) is unclear, however. To better understand the neuropathology associated with HIV and METH use, the patterns of neurodegeneration were assessed in HIV-positive METH users and in HIV-positive non-METH users. Patients in the study met criteria for inclusion and received neuromedical and postmortem neuropathologic examinations. Immunocytochemical and polymerase chain reaction analyses were performed to determine brain HIV levels and to exclude the presence of other viruses. METH-using patients with HIVE showed significantly lower gp41 scores and less severe forms of encephalitis but a higher frequency of ischemic events, a more pronounced loss of synaptophysin immunoreactivity, and a more severe microglial reaction than HIVE non-METH users. Furthermore, in METH-using patients with HIVE, extensive loss of calbindin (CB)-immunoreactive interneurons displaying phylopodial neuritic processes suggestive of aberrant sprouting was observed. Taken together, these studies indicate that the combined effects of METH and HIV selectively damage CB immunoreactive nonpyramidal neurons. In combination, METH and HIV may increase neuronal cell injury and death, thereby enhancing brain metabolic disturbances observed in clinical populations of HIV-positive METH abusers.
Langford
Dianne
D
Department of Pathology, University of California at San Francisco, La Jolla, CA 92093-0624, USA.
Adame
Anthony
A
Grigorian
Aline
A
Grant
Igor
I
McCutchan
J Allen
JA
Ellis
Ronald J
RJ
Marcotte
Thomas D
TD
Masliah
Eliezer
E
D015526:AIDS Dementia Complex / Q000276:immunology / Q000473:pathology*; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000473:pathology*; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000150:complications* / Q000473:pathology; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D018791:CD4 Lymphocyte Count; D064026:Calbindins; D005260:Female; D006679:HIV Seropositivity / Q000276:immunology / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010320:Parvalbumins / Q000032:analysis; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D019562:Viral Load
D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D008694:Methamphetamine