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

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

doi:10.1016/j.parkreldis.2008.04.012

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

Neuroscience

Research output: Contribution to journal › Review article › peer-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 language	English (US)
Pages (from-to)	S112-S115
Journal	Parkinsonism and Related Disorders
Volume	14
Issue number	SUPPL.2
DOIs	https://doi.org/10.1016/j.parkreldis.2008.04.012
State	Published - 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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10.1016/j.parkreldis.2008.04.012

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title = "Modeling PD pathogenesis in mice: Advantages of a chronic MPTP protocol",

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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note = "Funding Information: 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.). ",

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AU - Meredith, Gloria E.

AU - Totterdell, Susan

AU - Potashkin, Judith A.

AU - Surmeier, D. James

N1 - Funding Information: 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.).

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N2 - 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.

AB - 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.

KW - Alpha-synuclein

KW - Dopamine

KW - Grid test

KW - Isradipine

KW - L-type calcium channel

KW - Probenecid

KW - Substantia nigra

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

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