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(American Journal of Pathology. 2002;160:927-941.)
© 2002 American Society for Investigative Pathology

Regular Articles

Macrophages Relate Presynaptic and Postsynaptic Damage in Simian Immunodeficiency Virus Encephalitis

Stephanie J. Bissel*, Guoji Wang{dagger}, Mimi Ghosh*, Todd A. Reinhart*, Saverio Capuano, III*, Kelly Stefano Cole{ddagger}, Michael Murphey-Corb{ddagger}, Michael Piatak Jr.§, Jeffrey D. Lifson§ and Clayton A. Wiley{dagger}

From the Department of Infectious Diseases andMicrobiology,*
Graduate School of Public Health, and theDepartments of Pathology{dagger}
and MolecularGenetics and Microbiology,{ddagger}
University ofPittsburgh School of Medicine, Pittsburgh, Pennsylvania; and theLaboratory of Retroviral Pathogenesis,§
AIDSVaccine Program, Science Applications International CorporationFrederick, National Cancer Institute at Frederick, Frederick, Maryland

Neurodegeneration observed in lentiviral-associated encephalitis has been linked to viral-infected and -activated central nervous system macrophages. Wehypothesized that lentivirus, macrophages, or both lentivirus and macrophages within distinct microenvironments mediate synaptic damage. Using the simian immunodeficiency virus (SIV)-infected macaque model, we assessed the relationship between virus, macrophages, and neurological damage in multiple brain regions using laser confocal microscopy. In SIV-infected macaques with SIV encephalitis (SIVE), brain tissue concentrations of SIV RNA were 5 orders of magnitude greater than that observed in nonencephalitic animals. In SIVE, staining for postsynaptic protein microtubule-associated protein-2 was significantly decreased in the caudate, hippocampus, and frontal cortical gray matter compared to nonencephalitic controls, whereas staining for presynaptic protein synaptophysin was decreased in SIV-infectedmacaques with and without encephalitis. These data suggest that presynaptic damage occurs independent of pathological changes associated with SIVE, whereas postsynaptic damage is more tightly linked to regional presence of both activated and infected macrophages.




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