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Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice.

Petersén, Åsa LU ; Puschban, Zoe LU ; Lotharius, Julie LU ; NicNiocaill, B; Wiekop, P; O'Connor, W T and Brundin, Patrik LU (2002) In Neurobiology of Disease 11(1). p.134-146
Abstract
The present multidisciplinary study examined nigrostriatal dopamine and striatal amino acid transmission in the R6/1 line of transgenic Huntington's disease (HD) mice expressing exon 1 of the HD gene with 115 CAG repeats. Although the number of tyrosine hydroxylase-positive neurons was not reduced and nigrostriatal connectivity remained intact in 16-week-old R6/1 mice, the size of tyrosine hydroxylase-positive neurons in the substantia nigra was reduced by 15%, and approximately 30% of these cells exhibited aggregated huntingtin. In addition, using in vivo microdialysis, we found that basal extracellular striatal dopamine levels were reduced by 70% in R6/1 mice compared to their wild-type littermates. Intrastriatal perfusion with malonate... (More)
The present multidisciplinary study examined nigrostriatal dopamine and striatal amino acid transmission in the R6/1 line of transgenic Huntington's disease (HD) mice expressing exon 1 of the HD gene with 115 CAG repeats. Although the number of tyrosine hydroxylase-positive neurons was not reduced and nigrostriatal connectivity remained intact in 16-week-old R6/1 mice, the size of tyrosine hydroxylase-positive neurons in the substantia nigra was reduced by 15%, and approximately 30% of these cells exhibited aggregated huntingtin. In addition, using in vivo microdialysis, we found that basal extracellular striatal dopamine levels were reduced by 70% in R6/1 mice compared to their wild-type littermates. Intrastriatal perfusion with malonate in R6/1 mice resulted in a short-lasting, attenuated increase in local dopamine release compared to wild-type mice. Furthermore, the size of the malonate-induced striatal lesion was 80% smaller in these animals. Taken together, these findings suggest that a functional deficit in nigrostriatal dopamine transmission may contribute to the behavioral phenotype and the resistance to malonate-induced neurotoxicity characteristic of R6/1 HD mice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Huntington's disease, malonate, microdialysis, substantia nigra, striatum, dopamine
in
Neurobiology of Disease
volume
11
issue
1
pages
134 - 146
publisher
Elsevier
external identifiers
  • pmid:12460553
  • wos:000179314100012
  • scopus:0036453663
ISSN
0969-9961
DOI
10.1006/nbdi.2002.0534
language
English
LU publication?
yes
id
24e5baf3-7e1e-445a-b6ce-7601832b59f1 (old id 111668)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12460553&dopt=Abstract
date added to LUP
2007-06-26 12:32:58
date last changed
2017-12-10 03:56:25
@article{24e5baf3-7e1e-445a-b6ce-7601832b59f1,
  abstract     = {The present multidisciplinary study examined nigrostriatal dopamine and striatal amino acid transmission in the R6/1 line of transgenic Huntington's disease (HD) mice expressing exon 1 of the HD gene with 115 CAG repeats. Although the number of tyrosine hydroxylase-positive neurons was not reduced and nigrostriatal connectivity remained intact in 16-week-old R6/1 mice, the size of tyrosine hydroxylase-positive neurons in the substantia nigra was reduced by 15%, and approximately 30% of these cells exhibited aggregated huntingtin. In addition, using in vivo microdialysis, we found that basal extracellular striatal dopamine levels were reduced by 70% in R6/1 mice compared to their wild-type littermates. Intrastriatal perfusion with malonate in R6/1 mice resulted in a short-lasting, attenuated increase in local dopamine release compared to wild-type mice. Furthermore, the size of the malonate-induced striatal lesion was 80% smaller in these animals. Taken together, these findings suggest that a functional deficit in nigrostriatal dopamine transmission may contribute to the behavioral phenotype and the resistance to malonate-induced neurotoxicity characteristic of R6/1 HD mice.},
  author       = {Petersén, Åsa and Puschban, Zoe and Lotharius, Julie and NicNiocaill, B and Wiekop, P and O'Connor, W T and Brundin, Patrik},
  issn         = {0969-9961},
  keyword      = {Huntington's disease,malonate,microdialysis,substantia nigra,striatum,dopamine},
  language     = {eng},
  number       = {1},
  pages        = {134--146},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice.},
  url          = {http://dx.doi.org/10.1006/nbdi.2002.0534},
  volume       = {11},
  year         = {2002},
}