title: Macrophages relate presynaptic and postsynaptic damage in simian immunodeficiency virus encephalitis.
abstract: Neurodegeneration observed in lentiviral-associated encephalitis has been linked to viral-infected and -activated central nervous system macrophages. We hypothesized 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-infected macaques 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.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bissel
authors.forename: Guoji
authors.initials: G
authors.lastname: Wang
authors.forename: Mimi
authors.initials: M
authors.lastname: Ghosh
authors.forename: Todd A
authors.initials: TA
authors.lastname: Reinhart
authors.forename: Saverio
authors.initials: S
authors.lastname: Capuano
authors.forename: Kelly
authors.initials: K
authors.lastname: Stefano Cole
authors.forename: Michael
authors.initials: M
authors.lastname: Murphey-Corb
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak Jr
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018792:Encephalitis, Viral / Q000276:immunology / Q000473:pathology*; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D018613:Microscopy, Confocal; D017729:Presynaptic Terminals / Q000473:pathology; D012367:RNA, Viral / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification
chemical_list: D012367:RNA, Viral