Proton Magnetic Resonance Spectroscopy Reveals Neuroprotection by Oral Minocycline in a Nonhuman Primate Model of Accelerated NeuroAIDS
View/ Open
Author
Bombardier, Jeffrey P.
Annamalai, Lakshmanan
Burdo, Tricia H.
Fell, Robert
Hakimelahi, Reza
He, Julian
Autissier, Patrick
Masliah, Eliezer
Williams, Kenneth C.
González, R. Gilberto
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1371/journal.pone.0010523Metadata
Show full item recordCitation
Ratai, Eva-Maria, Jeffrey P. Bombardier, Chan-Gyu Joo, Lakshmanan Annamalai, Tricia H. Burdo, Jennifer Campbell, Robert Fell, et al. 2010. Proton Magnetic Resonance Spectroscopy Reveals Neuroprotection by Oral Minocycline in a Nonhuman Primate Model of Accelerated NeuroAIDS. PLoS ONE 5(5): e10523.Abstract
Background: Despite the advent of highly active anti-retroviral therapy (HAART), HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV) macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury. Methodology/Principal Findings: Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi). Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN), microtubule-associated protein 2 (MAP2), and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr), which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals. Conclusions/Significance: In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866543/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:5355308
Collections
- HMS Scholarly Articles [17917]
Contact administrator regarding this item (to report mistakes or request changes)