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

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 D(1) dopamine/DARPP-32 signaling cascade. These presymptomatic defects may contribute to HD pathology.

authors

Bibb JA,Yan Z,Svenningsson P,Snyder GL,Pieribone VA,Horiuchi A,Nairn AC,Messer A,Greengard P

doi

10.1073/pnas.120166397

keywords:

subject

Has Abstract

pub_date

2000-06-06 00:00:00

pages

6809-14

issue

12

eissn

0027-8424

issn

1091-6490

pii

120166397

journal_volume

97

pub_type

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