Sustained striatal ciliary neurotrophic factor expression negatively affects behavior and gene expression in normal and R6/1 mice
dc.contributor.author | Denovan-Wright, Eileen M. | en_US |
dc.contributor.author | Attis, Marissa | en_US |
dc.contributor.author | Rodriguez-Lebron, Edgardo | en_US |
dc.contributor.author | Mandel, Ronald J. | en_US |
dc.date.accessioned | 2008-06-04T14:38:18Z | |
dc.date.available | 2009-06-01T20:08:52Z | en_US |
dc.date.issued | 2008-06 | en_US |
dc.identifier.citation | Denovan-Wright, Eileen M.; Attis, Marissa; Rodriguez-Lebron, Edgardo; Mandel, Ronald J. (2008). "Sustained striatal ciliary neurotrophic factor expression negatively affects behavior and gene expression in normal and R6/1 mice." Journal of Neuroscience Research 86(8): 1748-1757. <http://hdl.handle.net/2027.42/58641> | en_US |
dc.identifier.issn | 0360-4012 | en_US |
dc.identifier.issn | 1097-4547 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/58641 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18293418&dopt=citation | en_US |
dc.description.abstract | Huntington's disease (HD) is a neurodegenerative disorder caused by an elongation of CAG repeats in the HD gene, which encodes a mutant copy of huntingtin with an expanded polyglutatmine repeat. Individuals who are affected by the disease suffer from motor, cognitive, and emotional impairments. Levels of certain striatal-enriched mRNAs decrease in both HD patients and transgenic HD mice prior to the development of motor symptoms and neuronal cell death. Ciliary neurotrophic factor (CNTF) has been shown to protect neurons against chemically induced toxic insults in vitro and in vivo. To test the hypothesis that CNTF might protect neurons from the negative effects of the mutant huntingtin protein in vivo, CNTF was continuously expressed following transduction of the striatum by recombinant adeno-associated viral vectors (rAAV2). Wild-type and R6/1 HD transgenic (R6/1) mice that received bilateral or unilateral intrastriatal injections of rAAV2-CNTF experienced weight loss. The CNTF-treated R6/1 HD transgenic mice experienced motor impairments at an earlier age than expected compared with age-matched control R6/1 HD transgenic animals. CNTF also caused abnormal behavior in WT mice. In addition to behavioral impairments, in situ hybridization showed that, in both WT and R6/1 mice, CNTF expression caused a significant decrease in the levels of striatal-enriched transcripts. Overall, continuous expression of striatal CNTF at the dose mediated by the expression cassette used in this study was detrimental to HD and wild-type mice. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 207041 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Neuroscience, Neurology and Psychiatry | en_US |
dc.title | Sustained striatal ciliary neurotrophic factor expression negatively affects behavior and gene expression in normal and R6/1 mice | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbsecondlevel | Neurosciences | en_US |
dc.subject.hlbsecondlevel | Psychology | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Social Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Neurology, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada | en_US |
dc.contributor.affiliationother | Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada | en_US |
dc.contributor.affiliationother | Department of Neuroscience, University of Florida McKnight Brain Institute and Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida ; Department of Neuroscience, University of Florida McKnight Brain Institute and Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL 32610-0244 | en_US |
dc.identifier.pmid | 18293418 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/58641/1/21636_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/jnr.21636 | en_US |
dc.identifier.source | Journal of Neuroscience Research | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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