Mutant Huntingtin Causes a Selective Decrease in the Expression of Synaptic Vesicle Protein 2C

摘要: Huntington's disease (HD) is a neurodegenerative caused by polyglutamine expansion in the huntingtin (Htt) protein. Mutant Htt causes synaptic transmission dysfunctions interfering expression of proteins, leading to early HD symptoms. Synaptic vesicle proteins 2 (SV2s), family including 3 members, SV2A, SV2B, and SV2C, plays important roles physiology. Here, we investigated whether SV2s affected mutant brains transgenic (TG) mice Neuro2a mouse neuroblastoma cells (N2a cells) expressing Htt. Western blot analysis showed that protein levels SV2A SV2B were not significantly changed TG with 82 glutamine repeats. However, brain there was dramatic decrease level which has restricted distribution pattern regions particularly vulnerable HD. Immunostaining revealed immunoreactivity SV2C progressively weakened basal ganglia hippocampus mice. RT-PCR demonstrated mRNA declined without detectable changes indicating selectively inhibits transcriptional SV2C. Furthermore, found only inhibited N2a containing 120 These findings suggest dysfunction results from Htt-mediated inhibition expression. data also imply decreased contribute region-selective pathology