Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice

Abstract Time-of-day effects have been noted in a wide variety of cognitive behavioral tests, and perturbation of the circadian system, either at the level of the master clock in the SCN or downstream, impairs hippocampus-dependent learning and memory. A number of kinases, including the serine-threo...

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Autores principales:	Heather Mahoney, Emily Peterson, Hannah Justin, David Gonzalez, Christopher Cardona, Korey Stevanovic, John Faulkner, Amara Yunus, Alexandra Portugues, Amy Henriksen, Camden Burns, Cameron McNeill, Joshua Gamsby, Danielle Gulick
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f756b73ad8f84855a26f61f1129e93c4
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spelling	oai:doaj.org-article:f756b73ad8f84855a26f61f1129e93c42021-12-02T13:35:03ZInhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice10.1038/s41598-021-83957-92045-2322https://doaj.org/article/f756b73ad8f84855a26f61f1129e93c42021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83957-9https://doaj.org/toc/2045-2322Abstract Time-of-day effects have been noted in a wide variety of cognitive behavioral tests, and perturbation of the circadian system, either at the level of the master clock in the SCN or downstream, impairs hippocampus-dependent learning and memory. A number of kinases, including the serine-threonine casein kinase 1 (CK1) isoforms CK1δ/ε, regulate the timing of the circadian period through post-translational modification of clock proteins. Modulation of these circadian kinases presents a novel treatment direction for cognitive deficits through circadian modulation. Here, we tested the potential for PF-670462, a small molecule inhibitor of CK1δ/ε, to improve cognitive performance in C57BL/6J mice in an array of behavioral tests. Compared to vehicle-treated mice tested at the same time of the circadian day, mice treated with PF-670462 displayed better recall of contextual fear conditioning, made fewer working memory errors in the radial arm water maze, and trained more efficiently in the Morris Water Maze. These benefits were accompanied by increased expression of activity-regulated cytoskeleton-associated protein (Arc) in the amygdala in response to an acute learning paradigm. Our results suggest the potential utility of CK1δ/ε inhibition in improving time-of-day cognitive performance.Heather MahoneyEmily PetersonHannah JustinDavid GonzalezChristopher CardonaKorey StevanovicJohn FaulknerAmara YunusAlexandra PortuguesAmy HenriksenCamden BurnsCameron McNeillJoshua GamsbyDanielle GulickNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heather Mahoney Emily Peterson Hannah Justin David Gonzalez Christopher Cardona Korey Stevanovic John Faulkner Amara Yunus Alexandra Portugues Amy Henriksen Camden Burns Cameron McNeill Joshua Gamsby Danielle Gulick Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice
description	Abstract Time-of-day effects have been noted in a wide variety of cognitive behavioral tests, and perturbation of the circadian system, either at the level of the master clock in the SCN or downstream, impairs hippocampus-dependent learning and memory. A number of kinases, including the serine-threonine casein kinase 1 (CK1) isoforms CK1δ/ε, regulate the timing of the circadian period through post-translational modification of clock proteins. Modulation of these circadian kinases presents a novel treatment direction for cognitive deficits through circadian modulation. Here, we tested the potential for PF-670462, a small molecule inhibitor of CK1δ/ε, to improve cognitive performance in C57BL/6J mice in an array of behavioral tests. Compared to vehicle-treated mice tested at the same time of the circadian day, mice treated with PF-670462 displayed better recall of contextual fear conditioning, made fewer working memory errors in the radial arm water maze, and trained more efficiently in the Morris Water Maze. These benefits were accompanied by increased expression of activity-regulated cytoskeleton-associated protein (Arc) in the amygdala in response to an acute learning paradigm. Our results suggest the potential utility of CK1δ/ε inhibition in improving time-of-day cognitive performance.
format	article
author	Heather Mahoney Emily Peterson Hannah Justin David Gonzalez Christopher Cardona Korey Stevanovic John Faulkner Amara Yunus Alexandra Portugues Amy Henriksen Camden Burns Cameron McNeill Joshua Gamsby Danielle Gulick
author_facet	Heather Mahoney Emily Peterson Hannah Justin David Gonzalez Christopher Cardona Korey Stevanovic John Faulkner Amara Yunus Alexandra Portugues Amy Henriksen Camden Burns Cameron McNeill Joshua Gamsby Danielle Gulick
author_sort	Heather Mahoney
title	Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice
title_short	Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice
title_full	Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice
title_fullStr	Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice
title_full_unstemmed	Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice
title_sort	inhibition of casein kinase 1 δ/ε improves cognitive performance in adult c57bl/6j mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f756b73ad8f84855a26f61f1129e93c4
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Inhibition of casein kinase 1 δ/ε improves cognitive performance in adult C57BL/6J mice

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