Modeling PD pathogenesis in mice: Advantages of a chronic MPTP protocol

Gloria E. Meredith*, Susan Totterdell, Judith A. Potashkin, D. James Surmeier

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

179 Scopus citations

Abstract

Formidable challenges for Parkinson's disease (PD) research are to understand the processes underlying nigrostriatal degeneration and how to protect dopamine neurons. Fundamental research relies on good animal models that demonstrate the pathological hallmarks and motor deficits of PD. Using a chronic regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p) in mice, dopamine cell loss exceeds 60%, extracellular glutamate is elevated, cytoplasmic inclusions are formed and inflammation is chronic. Nevertheless, isradipine, an L-type calcium-channel blocker, attenuates the degeneration. These data support the validity of the MPTP/p model for unravelling the degenerative processes in PD and testing therapies that slow their progress.

Original languageEnglish (US)
Pages (from-to)S112-S115
JournalParkinsonism and Related Disorders
Volume14
Issue numberSUPPL.2
DOIs
StatePublished - Jul 2008

Funding

Funding was provided by the United States Army Medical Research and Material Command (grant number W81XWH-05-1-0580 to G.E.M.) and the NIH (grants NS41799 to G.E.M., and NS047085 to D.J.S.).

Keywords

  • Alpha-synuclein
  • Dopamine
  • Grid test
  • Isradipine
  • L-type calcium channel
  • Probenecid
  • Substantia nigra

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neurology

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