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

In Huntington's disease (HD), mutation of huntingtin causes selective neuro degeneration of dopaminoceptive striatal medium spiny neurons. Transgenic: Ho model mice that express a portion of the disease-causing form of human h untingtin develop a behavioral phenotype that suggests dysfunction of dopam inergic neurotransmission, Here we show that presymtomatic mice have severe deficiencies in dopamine signaling in the striatum, These include selectiv e reductions in total levels of dopamine- and cAMP-regulated phosphoprotein , MI 32 kDA (DARPP-32) and other dopamine-regulated phosphoprotein markers of medium spiny neurons, HD mice also show defects in dopamine-regulated io n channels and in the D-1 dopamine/DARPP-32 signaling cascade. These presym ptomatic defects may contribute to Ho pathology.