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Title: | The sGC stimulator BAY-747 and activator runcaciguat can enhance memory in vivo via differential hippocampal plasticity mechanisms | Authors: | NELISSEN, Ellis Possemis, Nina Van Goethem, Nick P. SCHEPERS, Melissa Mulder-Jongen, Danielle A. J. Dietz, Lisa JANSSEN, Wiebke Gerisch, Michael Huser, Jorg Sandner, Peter VANMIERLO, Tim Prickaerts, Jos |
Issue Date: | 2022 | Publisher: | NATURE PORTFOLIO | Source: | Scientific Reports, 12 (1) (Art N° 3589) | Abstract: | Soluble guanylate cyclase (sGC) requires a heme-group bound in order to produce cGMP, a second messenger involved in memory formation, while heme-free sGC is inactive. Two compound classes can increase sGC activity: sGC stimulators acting on heme-bound sGC, and sGC activators acting on heme-free sGC. In this rodent study, we investigated the potential of the novel brain-penetrant sGC stimulator BAY-747 and sGC activator runcaciguat to enhance long-term memory and attenuate short-term memory deficits induced by the NOS-inhibitor L-NAME. Furthermore, hippocampal plasticity mechanisms were investigated. In vivo, oral administration of BAY-747 and runcaciguat to male Wistar rats enhanced memory acquisition in the object location task (OLT), while only BAY-747 reversed L-NAME induced memory impairments in the OLT. Ex vivo, both BAY-747 and runcaciguat enhanced hippocampal GluA1-containing AMPA receptor (AMPAR) trafficking in a chemical LTP model for memory acquisition using acute mouse hippocampal slices. In vivo only runcaciguat acted on the glutamatergic AMPAR system in hippocampal memory acquisition processes, while for BAY-747 the effects on the neurotrophic system were more pronounced as measured in male mice using western blot. Altogether this study shows that sGC stimulators and activators have potential as cognition enhancers, while the underlying plasticity mechanisms may determine disease-specific effectiveness. | Notes: | Nelissen, E; Prickaerts, J (corresponding author), Maastricht Univ, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci MHeNS, Univ Singel 50, NL-6229 ER Maastricht, Netherlands. e.nelissen@maastrichtuniversity.nl; jos.prickaerts@maastrichtuniversity.nl |
Document URI: | http://hdl.handle.net/1942/37079 | ISSN: | 2045-2322 | e-ISSN: | 2045-2322 | DOI: | 10.1038/s41598-022-07391-1 | ISI #: | WOS:000764883800038 | Rights: | The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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The sGC stimulator BAY-747 and activator runcaciguat can enhance memory in vivo via differential hippocampal plasticity mechanisms.pdf | Published version | 1.69 MB | Adobe PDF | View/Open |
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