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

Smith, Ruben LU ; Petersén, Åsa LU ; Bates, Gillian P; Brundin, Patrik LU and Li, Jia-Yi LU (2005) In Neurobiology of Disease 20(3). p.673-684
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
vesicle protein, huntingtin, synaptic dysfunction, synapse, mouse, Huntington's disease, R6/1, CAG repeal, neurodegeneration, polyglutamine, rabphilin, exocytosis
in
Neurobiology of Disease
volume
20
issue
3
pages
673 - 684
publisher
Elsevier
external identifiers
  • pmid:15967669
  • wos:000233739100005
  • scopus:24344444735
ISSN
0969-9961
DOI
10.1016/j.nbd.2005.05.008
language
English
LU publication?
yes
id
ea149b2d-1546-42aa-a6fa-92273b6c691f (old id 139902)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15967669&query_hl=50
date added to LUP
2007-07-19 13:46:25
date last changed
2017-10-22 03:52:49
@article{ea149b2d-1546-42aa-a6fa-92273b6c691f,
  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       = {Smith, Ruben and Petersén, Åsa and Bates, Gillian P and Brundin, Patrik and Li, Jia-Yi},
  issn         = {0969-9961},
  keyword      = {vesicle protein,huntingtin,synaptic dysfunction,synapse,mouse,Huntington's disease,R6/1,CAG repeal,neurodegeneration,polyglutamine,rabphilin,exocytosis},
  language     = {eng},
  number       = {3},
  pages        = {673--684},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Depletion of rabphilin 3A in a transgenic mouse model (R6/1) of Huntington's disease, a possible culprit in synaptic dysfunction.},
  url          = {http://dx.doi.org/10.1016/j.nbd.2005.05.008},
  volume       = {20},
  year         = {2005},
}