title: 14-3-3 Protein in CSF reflects SIV-mediated pre-synaptic damage.
abstract: HIV-associated neurocognitive disorders (HAND) remain prevalent despite effective combined anti-retroviral therapy (cART). Cognitive function has been shown to inversely correlate with decreased synaptic and dendritic density. In this study, macaques inoculated with SIV were examined over a 3-month course of infection to characterize the appearance of the neuronal damage marker 14-3-3 protein in CSF and to determine whether CSF 14-3-3 levels directly reflected synaptic alterations. SIV-infected macaques with 14-3-3 in CSF had significantly lower levels of the presynaptic protein synaptophysin in cortical grey matter. Synaptophysin levels were inversely correlated with amount of SIV RNA in the CNS. In contrast, levels of 14-3-3 in CSF did not correspond with either alterations in levels of the postsynaptic protein PSD-95 or viral replication in the brain. These findings suggest that the appearance of 14-3-3 in CSF during asymptomatic infection reflects pre-synaptic damage in SIV-infected macaques and thus may serve as a marker of the early synaptic alterations that underlie HIV-induced neurocognitive impairment.
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD 21205, USA. jmankows@jhmi.edu.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Helke
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Queen
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D020805:Central Nervous System Viral Diseases / Q000134:cerebrospinal fluid* / Q000821:virology; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000378:metabolism; D007150:Immunohistochemistry; D008251:Macaca; D009419:Nerve Tissue Proteins / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid* / Q000821:virology; D016708:Synaptophysin / Q000032:analysis; D019562:Viral Load
chemical_list: D048948:14-3-3 Proteins; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D012367:RNA, Viral; D016708:Synaptophysin