Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington's disease transgenic mice prior to the onset of motor symptoms.

摘要: Inheritance of a single copy the gene encoding huntingtin (HD) with an expanded polyglutamine-encoding CAG repeat leads to neuronal dysfunction, neurodegeneration and development symptoms Huntington's disease (HD). We have found that steady-state mRNA levels two members phosphodiesterase (PDE) multi-gene family decrease over time in striatum R6 transgenic HD mice relative age-matched wild-type littermates. Phosphodiesterase 10A (PDE10A) protein decline R6/1 R6/2 prior motor symptom development. The rate reduction PDE10A correlates message is more rapid compared mice. Both mRNA, therefore, minimum onset overt physical both strains Moreover, are decreased caudate-putamen grade 3 patients neuropathologically normal controls. Striatal PDE1B also mice; however, striatal (>60%) was greater than observed for immediately preceded symptoms. In contrast, PDE4A relatively low do not differ between This suggests regulation PDE1B, but PDE4A, dependent on expression or number repeats within human transgene. loss activity may lead dysregulation cyclic adenosine monophosphate (cAMP) guanosine (cGMP) striatum, region brain contributes control movement cognition.