Soluble guanylate cyclase stimulator riociguat improves spatial memory in mice via peripheral mechanisms
Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved..
Soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) signalling is important for healthy memory function and a healthy vascular system. Targeting sGC-cGMP signalling can therefore be a potential strategy to enhance memory processes. sGC can be targeted by using agonists, such as sGC stimulator riociguat. Therefore, this study aimed to target sGC using riociguat to investigate its acute effects on memory function and neuronal plasticity in mice. The effects of riociguat on long-term memory and a biperiden-induced memory deficit model for assessing short-term memory were tested in the object location task, and working memory was tested in the Y-maze continuous alternation task. Pharmacokinetic measurements were performed within brain tissue of mice, and hippocampal plasticity measures were assessed using western blotting. Acute oral administration with a low dose of 0.03 mg/kg riociguat was able to enhance working-, short-, and long-term spatial memory. Under cerebral vasoconstriction higher doses of riociguat were still effective on memory. Pharmacokinetic measurements revealed poor brain penetration of riociguat and its metabolite M-1. Increased activation of VASP was found, while no effects were found on other memory-related hippocampal plasticity measures. Memory enhancing effects of riociguat are most likely regulated by vascular peripheral effects on cGMP signalling. Yet, further research is needed to investigate the possible contribution of hemodynamic or metabolic effects of sGC stimulators on memory performance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:788 |
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| Enthalten in: |
Neuroscience letters - 788(2022) vom: 25. Sept., Seite 136840 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nelissen, Ellis [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.09.2022 Date Revised 15.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neulet.2022.136840 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) signalling is important for healthy memory function and a healthy vascular system. Targeting sGC-cGMP signalling can therefore be a potential strategy to enhance memory processes. sGC can be targeted by using agonists, such as sGC stimulator riociguat. Therefore, this study aimed to target sGC using riociguat to investigate its acute effects on memory function and neuronal plasticity in mice. The effects of riociguat on long-term memory and a biperiden-induced memory deficit model for assessing short-term memory were tested in the object location task, and working memory was tested in the Y-maze continuous alternation task. Pharmacokinetic measurements were performed within brain tissue of mice, and hippocampal plasticity measures were assessed using western blotting. Acute oral administration with a low dose of 0.03 mg/kg riociguat was able to enhance working-, short-, and long-term spatial memory. Under cerebral vasoconstriction higher doses of riociguat were still effective on memory. Pharmacokinetic measurements revealed poor brain penetration of riociguat and its metabolite M-1. Increased activation of VASP was found, while no effects were found on other memory-related hippocampal plasticity measures. Memory enhancing effects of riociguat are most likely regulated by vascular peripheral effects on cGMP signalling. Yet, further research is needed to investigate the possible contribution of hemodynamic or metabolic effects of sGC stimulators on memory performance | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Cognition | |
| 650 | 4 | |a Guanosine monophosphate | |
| 650 | 4 | |a Guanylyl cyclase | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Spatial memory | |
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| 700 | 1 | |a Argyrousi, Elentina K |e verfasserin |4 aut | |
| 700 | 1 | |a van Goethem, Nick P |e verfasserin |4 aut | |
| 700 | 1 | |a Heckman, Pim R A |e verfasserin |4 aut | |
| 700 | 1 | |a Paes, Dean |e verfasserin |4 aut | |
| 700 | 1 | |a Mulder-Jongen, Danielle A J |e verfasserin |4 aut | |
| 700 | 1 | |a Ramaekers, Johannes G |e verfasserin |4 aut | |
| 700 | 1 | |a Blokland, Arjan |e verfasserin |4 aut | |
| 700 | 1 | |a Schmidt, Harald H H W |e verfasserin |4 aut | |
| 700 | 1 | |a Prickaerts, Jos |e verfasserin |4 aut | |
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