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http://hdl.handle.net/2445/49179
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DC Field | Value | Language |
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dc.contributor.author | Saavedra, Ana | - |
dc.contributor.author | Giralt Torroella, Albert | - |
dc.contributor.author | Arumí, Helena | - |
dc.contributor.author | Alberch i Vié, Jordi, 1959- | - |
dc.contributor.author | Pérez Navarro, Esther | - |
dc.date.accessioned | 2014-01-27T12:38:46Z | - |
dc.date.available | 2014-01-27T12:38:46Z | - |
dc.date.issued | 2013-09-05 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2445/49179 | - |
dc.description.abstract | Huntington"s disease (HD) patients and mouse models show learning and memory impairment associated with hippocampal dysfunction. The neuronal nitric oxide synthase/3',5'-cyclic guanosine monophosphate (nNOS/cGMP) pathway is implicated in synaptic plasticity, and in learning and memory processes. Here, we examined the nNOS/cGMP pathway in the hippocampus of HD mice to determine whether it can be a good therapeutic target for cognitive improvement in HD. We analyzed hippocampal nNOS and phosphodiesterase (PDE) 5 and 9 levels in R6/1 mice, and cGMP levels in the hippocampus of R6/1, R6/2 and Hdh Q7/Q111 mice, and of HD patients. We also investigated whether sildenafil, a PDE5 inhibitor, could improve cognitive deficits in R6/1 mice. We found that hippocampal cGMP levels were 3-fold lower in 12-week-old R6/1 mice, when they show deficits in object recognition memory and in passive avoidance learning. Consistent with hippocampal cGMP levels, nNOS levels were down-regulated, while there were no changes in the levels of PDE5 and PDE9 in R6/1 mice. A single intraperitoneal injection of sildenafil (3 mg/Kg) immediately after training increased cGMP levels, and improved memory in R6/1 mice, as assessed by using the novel object recognition and the passive avoidance test. Importantly, cGMP levels were also reduced in R6/2 mouse and human HD hippocampus. Therefore, the regulation of hippocampal cGMP levels can be a suitable treatment for cognitive impairment in HD. | - |
dc.format.extent | 10 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0073664 | - |
dc.relation.ispartof | PLoS One, 2013, vol. 8, num. 9, p. e73664 | - |
dc.relation.uri | http://dx.doi.org/10.1371/journal.pone.0073664 | - |
dc.rights | cc-by (c) Saavedra, A. et al., 2013 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Corea de Huntington | - |
dc.subject.classification | Neurotransmissió | - |
dc.subject.classification | Teràpia genètica | - |
dc.subject.classification | Experimentació animal | - |
dc.subject.other | Huntington's chorea | - |
dc.subject.other | Neural transmission | - |
dc.subject.other | Gene therapy | - |
dc.subject.other | Animal experimentation | - |
dc.title | Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington's Disease | eng |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 628808 | - |
dc.date.updated | 2014-01-27T10:54:00Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 24040016 | - |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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628808.pdf | 676.53 kB | Adobe PDF | View/Open |
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