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.
Current HIV Research
Title:14-3-3 Protein in CSF Reflects SIV-Mediated Pre-Synaptic Damage
Volume: 11 Issue: 4
Author(s): Kristi L. Helke, Suzanne E. Queen and Joseph L. Mankowski
Affiliation:
Keywords: 14-3-3, CSF, HIV, PSD-95, SIV, synaptophysin.
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.
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Cite this article as:
Helke L. Kristi, Queen E. Suzanne and Mankowski L. Joseph, 14-3-3 Protein in CSF Reflects SIV-Mediated Pre-Synaptic Damage, Current HIV Research 2013; 11 (4) . https://dx.doi.org/10.2174/1570162X1131100049
DOI https://dx.doi.org/10.2174/1570162X1131100049 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
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