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Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease
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 proc...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764028/ https://www.ncbi.nlm.nih.gov/pubmed/24040016 http://dx.doi.org/10.1371/journal.pone.0073664 |
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author | Saavedra, Ana Giralt, Albert Arumí, Helena Alberch, Jordi Pérez-Navarro, Esther |
author_facet | Saavedra, Ana Giralt, Albert Arumí, Helena Alberch, Jordi Pérez-Navarro, Esther |
author_sort | Saavedra, Ana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3764028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37640282013-09-13 Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease Saavedra, Ana Giralt, Albert Arumí, Helena Alberch, Jordi Pérez-Navarro, Esther PLoS One Research Article 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. Public Library of Science 2013-09-05 /pmc/articles/PMC3764028/ /pubmed/24040016 http://dx.doi.org/10.1371/journal.pone.0073664 Text en © 2013 Saavedra et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Saavedra, Ana Giralt, Albert Arumí, Helena Alberch, Jordi Pérez-Navarro, Esther Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease |
title | Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease |
title_full | Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease |
title_fullStr | Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease |
title_full_unstemmed | Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease |
title_short | Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington’s Disease |
title_sort | regulation of hippocampal cgmp levels as a candidate to treat cognitive deficits in huntington’s disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764028/ https://www.ncbi.nlm.nih.gov/pubmed/24040016 http://dx.doi.org/10.1371/journal.pone.0073664 |
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