부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.nbd.2005.05.008 Byline: Ruben Smith (a), Asa Petersen (a), Gillian P. Bates (b), Patrik Brundin (a), Jia-Yi Li (a) Keywords: Huntington's disease; R6/1; Mouse; Synapse; Synaptic dysfunction; Exocytosis; Huntingtin; Vesicle protein; CAG repeat; Neurodegeneration; Polyglutamine; Rabphilin Abstract: Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by progressive psychiatric, cognitive, and motor disturbances. We studied the expression of synaptic vesicle proteins in the R6/1 transgenic mouse model of HD. We observed that the levels of rabphilin 3A, a protein involved in exocytosis, is substantially decreased in synapses of most brain regions in R6/1 mice. The appearance of the reduction coincides with the onset of motor deficits and behavioral disturbances. Double immunohistochemistry did not show colocalization between rabphilin 3A and huntingtin aggregates in the HD mice. Using in situ hybridization, we demonstrated that rabphilin 3A mRNA expression was substantially reduced in the R6/1 mouse cortex compared to wild-type mice. Our results indicate that a decrease in mRNA levels underlie the depletion of protein levels of rabphilin 3A, and we suggest that this reduction may be involved in causing impaired synaptic transmission in R6/1 mice. Author Affiliation: (a) Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A10, 221 84 Lund, Sweden (b) Medical and Molecular Genetics, GKT School of Medicine, London, UK Article History: Received 10 December 2004; Revised 8 April 2005; Accepted 2 May 2005