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The Journal of Neuroscience, September 20, 2006, 26(38):9750-9760; doi:10.1523/JNEUROSCI.2745-06.2006

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Neurobiology of Disease
A Specific Survival Response in Dopamine Neurons at Most Risk in Parkinson's Disease

Sachiko Murase and Ronald D. McKay

Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892

Correspondence should be addressed to Ronald D. McKay, 35 Convent Drive, MSC 4092, Bethesda, MD 20892. Email: mckay{at}codon.nih.gov

The specific expression of fibroblast growth factor 20 (FGF-20) in the adult substantia nigra and the association between FGF-20 mutations and Parkinson's disease provoked exploration of the function of this growth factor. We show by gain- and loss-of-function in vitro experiments that FGF-20 promotes survival and stimulates dopamine (DA) release in a calbindin-negative subset of cells that are preferentially lost in Parkinson's disease. FGF-20 selectively activates tyrosine hydroxylase in calbindin-negative neurons. In the adult substantia nigra, calbindin-negative neurons specifically express high levels of FGFR1 (FGF receptor 1). These data show that FGF signals to elevate DA levels and protect the specific midbrain neuron type at most risk in Parkinson's patients.

Key words: Parkinson's disease; fibroblast growth factor 20; dopamine; calbindin; midbrain; neurotrophic factor

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Received Feb. 7, 2006; revised Aug. 8, 2006; accepted Aug. 10, 2006.

Correspondence should be addressed to Ronald D. McKay, 35 Convent Drive, MSC 4092, Bethesda, MD 20892. Email: mckay{at}codon.nih.gov

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