Article thumbnail

Depletion of rabphilin 3A in a transgenic mouse model (R6/1) of Huntington's disease, a possible culprit in synaptic dysfunction.

By Ruben Smith, Åsa Petersén, Gillian P Bates, Patrik Brundin and Jia-Yi Li

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

Topics: Neurosciences, vesicle protein, huntingtin, synaptic dysfunction, synapse, mouse, Huntington's disease, R6/1, CAG repeal, neurodegeneration, polyglutamine, rabphilin, exocytosis
Publisher: 'Elsevier BV'
Year: 2005
DOI identifier: 10.1016/j.nbd.2005.05.008
OAI identifier: oai:lup.lub.lu.se:ea149b2d-1546-42aa-a6fa-92273b6c691f
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://dx.doi.org/10.1016/j.nb... (external link)
  • https://lup.lub.lu.se/record/1... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.