Severe Deficiencies in Dopamine Signaling in Presymptomatic Huntington's Disease Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2000 Jun 1

PMID 10829080

Citations 124

Authors

J A Bibb

Z Yan

P Svenningsson

G L Snyder

V A Pieribone

A Horiuchi

A C Nairn

A Messer

P Greengard

Affiliations

Soon will be listed here.

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.

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