Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice
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 redu...
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| Format: | Article |
| Language: | English |
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Elsevier
2002-10-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996102905346 |
| _version_ | 1829519159260610560 |
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| author | Å. Petersén Z. Puschban J. Lotharius B. NicNiocaill P. Wiekop W.T. O'Connor P. Brundin |
| author_facet | Å. Petersén Z. Puschban J. Lotharius B. NicNiocaill P. Wiekop W.T. O'Connor P. Brundin |
| author_sort | Å. Petersén |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T14:34:28Z |
| format | Article |
| id | doaj.art-75296625a5374c44a70235465afc744c |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T14:34:28Z |
| publishDate | 2002-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-75296625a5374c44a70235465afc744c2022-12-21T22:28:09ZengElsevierNeurobiology of Disease1095-953X2002-10-01111134146Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease MiceÅ. Petersén0Z. Puschban1J. Lotharius2B. NicNiocaill3P. Wiekop4W.T. O'Connor5P. Brundin6Section for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Sweden; Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; Section of Microdialysis, NeuroSearch, 93 Pederstrupvej, Ballerup, DenmarkSection for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Sweden; Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; Section of Microdialysis, NeuroSearch, 93 Pederstrupvej, Ballerup, DenmarkSection for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Sweden; Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; Section of Microdialysis, NeuroSearch, 93 Pederstrupvej, Ballerup, DenmarkSection for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Sweden; Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; Section of Microdialysis, NeuroSearch, 93 Pederstrupvej, Ballerup, DenmarkSection for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Sweden; Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; Section of Microdialysis, NeuroSearch, 93 Pederstrupvej, Ballerup, DenmarkSection for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Sweden; Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; Section of Microdialysis, NeuroSearch, 93 Pederstrupvej, Ballerup, DenmarkSection for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Sweden; Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland; Section of Microdialysis, NeuroSearch, 93 Pederstrupvej, Ballerup, DenmarkThe 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.http://www.sciencedirect.com/science/article/pii/S0969996102905346dopamineHuntington's diseasemalonatemicrodialysisstriatumsubstantia nigra |
| spellingShingle | Å. Petersén Z. Puschban J. Lotharius B. NicNiocaill P. Wiekop W.T. O'Connor P. Brundin Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice Neurobiology of Disease dopamine Huntington's disease malonate microdialysis striatum substantia nigra |
| title | Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice |
| title_full | Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice |
| title_fullStr | Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice |
| title_full_unstemmed | Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice |
| title_short | Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice |
| title_sort | evidence for dysfunction of the nigrostriatal pathway in the r6 1 line of transgenic huntington s disease mice |
| topic | dopamine Huntington's disease malonate microdialysis striatum substantia nigra |
| url | http://www.sciencedirect.com/science/article/pii/S0969996102905346 |
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