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Title: | Regulation of Hippocampal cGMP Levels as a Candidate to Treat Cognitive Deficits in Huntington's Disease |
Author: | Saavedra, Ana Giralt Torroella, Albert Arumí, Helena Alberch i Vié, Jordi, 1959- Pérez Navarro, Esther |
Keywords: | Corea de Huntington Neurotransmissió Teràpia genètica Experimentació animal Huntington's chorea Neural transmission Gene therapy Animal experimentation |
Issue Date: | 5-Sep-2013 |
Publisher: | Public Library of Science (PLoS) |
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. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0073664 |
It is part of: | PLoS One, 2013, vol. 8, num. 9, p. e73664 |
URI: | http://hdl.handle.net/2445/49179 |
Related resource: | http://dx.doi.org/10.1371/journal.pone.0073664 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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