Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice

James A. Bibb, Zhen Yan, Per Svenningsson, Gretchen L. Snyder, Vincent A. Pieribone, Atsuko Horiuchi, Angus C. Nairn, Anne Messer, Paul Greengard

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223 Scopus citations

Abstract

In Huntington's disease (HD), mutation of huntingtin causes selective neurodegeneration of dopaminoceptive striatal medium spiny neurons. Transgenic HD model mice that express a portion of the disease causing form of human huntingtin develop a behavioral phenotype that suggests dysfunction of dopaminergic neurotransmission. Here we show that presymtomatic mice have severe deficiencies in dopamine signaling in the striatum. These include selective reductions in total levels of dopamine- and cAMP-regulated phosphoprotein, M(r) 32 kDA (DARPP-32) and other dopamine-regulated phosphoprotein markers of medium spiny neurons. HD mice also show defects in dopamine-regulated ion channels and in the D1 dopamine/DARPP-32 signaling cascade. These presymptomatic defects may contribute to HD pathology.

Original languageEnglish (US)
Pages (from-to)6809-6814
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number12
DOIs
StatePublished - Jun 6 2000

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    Bibb, J. A., Yan, Z., Svenningsson, P., Snyder, G. L., Pieribone, V. A., Horiuchi, A., Nairn, A. C., Messer, A., & Greengard, P. (2000). Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice. Proceedings of the National Academy of Sciences of the United States of America, 97(12), 6809-6814. https://doi.org/10.1073/pnas.120166397