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

Kelly A. Meulendyke, Mikhail V. Pletnikov, Elizabeth L. Engle, Patrick M. Tarwater, David R. Graham, M. Christine Zink

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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, minocyclinetreated 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.

Original languageEnglish
Pages (from-to)454-464
Number of pages11
JournalJournal of NeuroImmune Pharmacology
Issue number2
StatePublished - Jun 2012

Bibliographical note

Funding Information:
Studies were supported by grants from the National Institute of Mental Health: R01 MH069116, R01 MH087233, and R01 MH085554. K.A.Meulendyke.M.V.Pletnikov.E.L.Engle. D. R. Graham.M. C. Zink (*) Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, 733 North Broadway Street, BRB 819, Baltimore, MD 21205, USA e-mail: mczink@jhmi.edu


  • Dopamine
  • HIV
  • Minocycline
  • Monoamine oxidase
  • Oxidative stress
  • SIV

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology


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