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Review
. 2008;14 Suppl 2(Suppl 2):S112-5.
doi: 10.1016/j.parkreldis.2008.04.012. Epub 2008 Jun 27.

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

Gloria E Meredith  1 , Susan Totterdell, Judith A Potashkin, D James Surmeier
Affiliations
Review

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

Gloria E Meredith et al. Parkinsonism Relat Disord. 2008.

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.

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Figures

Fig. 1
Fig. 1
Images of TH and alpha-synuclein immunoreactivity in the SNpc. (A) TH-immunoreactive neurons, (B) alpha-synuclein-immunoreactive puncta (note the varicosities of alpha-synuclein terminals), and (C) merged image showing the alpha-synuclein-immunoreactive granular inclusions in TH-immunoreactive neurons. Scale bar in A is valid for A, B and C, and equals 25μm.
Fig. 2
Fig. 2
Ultrastructural appearance of inclusions in the SNpc of MPTP/p-treated mice. (A) A TH-immunoreactive membrane-bound structure is filled with a proteinaceous deposit (black arrows) and an electron lucent lipid deposit (asterisk). Note extracellular parallel fibers (white arrows). (B) Proteinaceous (black arrows) cytoplasmic deposits and lipid (asterisk) in the SNpc. Scale bar in B is valid for A and B, and equals 0.5μm.
See this image and copyright information in PMC

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