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J Neuroimmune Pharmacol. 2012 Jun;7(2):454-64. doi: 10.1007/s11481-011-9332-1. Epub 2011 Dec 27.

Early minocycline treatment prevents a decrease in striatal dopamine in an SIV model of HIV-associated neurological disease.

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  • 1Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 733 North Broadway Street, Baltimore, MD 21205, USA.

Abstract

HIV-infected individuals, even with antiretroviral therapy, often display cognitive, behavioral and motor abnormalities and have decreased dopamine (DA) levels. Minocycline prevents encephalitis and neurodegeneration in SIV models, suggesting that it might also protect against nigrostriatal dopaminergic system dysfunction. Using an SIV/macaque model of HIV-associated CNS disease, we demonstrated that striatal levels of DA were significantly lower in macaques late in infection and that levels of the metabolite DOPAC also tended to be lower. DA levels declined more than its metabolites, indicating a dysregulation of DA production or catabolism. Minocycline treatment beginning at 12 but not 21 days postinoculation prevented striatal DA loss. DA decline was not due to direct loss of dopaminergic projections to the basal ganglia as there was no difference in tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter 2 or synaptophysin between minocycline-treated and untreated macaques. SIV-infected macaques had significantly higher monoamine oxidase (MAO) activity than uninfected macaques, although MAO activity was not affected by minocycline. Oxidative/nitrosative stress was examined by nitrotyrosine staining in the deep white matter and was lower in SIV-infected, minocycline-treated macaques compared with untreated macaques. These data suggest that minocycline, which has antioxidant activity, has a protective effect on DA homeostasis when administered at an appropriate time in SIV neuropathogenesis.

PMID:
22198699
[PubMed - indexed for MEDLINE]
PMCID:
PMC3354017
Free PMC Article
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