Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice
Proceedings of the National Academy of Sciences, 2000•National Acad Sciences
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 …
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 …
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, Mr 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.
National Acad Sciences