Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/111668
- author
- Petersén, Åsa LU ; Puschban, Zoe LU ; Lotharius, Julie LU ; NicNiocaill, B ; Wiekop, P ; O'Connor, W T and Brundin, Patrik LU
- organization
- publishing date
- 2002
- 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
- 2016-04-01 12:37:48
- date last changed
- 2022-04-06 00:59:50
@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}},
keywords = {{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}},
doi = {{10.1006/nbdi.2002.0534}},
volume = {{11}},
year = {{2002}},
}