Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice

Abstract The relationships among neuropeptide, calcitonin gene-related peptide (CGRP), and memory formation remain unclear. Here, we showed that the intracerebroventricular administration of CGRP impaired the traumatic fear memories, in a widely studied animal model of post-traumatic stress disorder...

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Autores principales:	Narumi Hashikawa-Hobara, Shuta Mishima, Chihiro Okujima, Youdai Shitanishi, Naoya Hashikawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa12b5d6b2b149528e0bf685a1be2b22
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spelling	oai:doaj.org-article:fa12b5d6b2b149528e0bf685a1be2b222021-12-02T17:04:07ZNpas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice10.1038/s41598-021-86556-w2045-2322https://doaj.org/article/fa12b5d6b2b149528e0bf685a1be2b222021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86556-whttps://doaj.org/toc/2045-2322Abstract The relationships among neuropeptide, calcitonin gene-related peptide (CGRP), and memory formation remain unclear. Here, we showed that the intracerebroventricular administration of CGRP impaired the traumatic fear memories, in a widely studied animal model of post-traumatic stress disorder. We found that CGRP administration suppressed fear memory by increasing neuronal PAS domain protein 4 (Npas4), phosphorylated histone deacetylase 5 (HDAC5), and protein kinase D (PKD). We also discovered that Npas4 knockdown inhibited CGRP-mediated fear memory. CGRP decreased the binding between HDAC5 and the Npas4 enhancer site and increased the binding between acetylated histone H3 and the Npas4 enhancer site. The pharmacological inhibition or knockdown of PKD attenuated the CGRP-mediated impairment of fear memory and the increased phosphorylation of HDAC5 and Npas4 expression. Our findings demonstrated that the CGRP-PKD pathway was associated with the histone H3 acetylation-Npas4 pathway. These results suggested a novel function for CGRP on fear memory, through epigenetic regulation.Narumi Hashikawa-HobaraShuta MishimaChihiro OkujimaYoudai ShitanishiNaoya HashikawaNature 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 Narumi Hashikawa-Hobara Shuta Mishima Chihiro Okujima Youdai Shitanishi Naoya Hashikawa Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice
description	Abstract The relationships among neuropeptide, calcitonin gene-related peptide (CGRP), and memory formation remain unclear. Here, we showed that the intracerebroventricular administration of CGRP impaired the traumatic fear memories, in a widely studied animal model of post-traumatic stress disorder. We found that CGRP administration suppressed fear memory by increasing neuronal PAS domain protein 4 (Npas4), phosphorylated histone deacetylase 5 (HDAC5), and protein kinase D (PKD). We also discovered that Npas4 knockdown inhibited CGRP-mediated fear memory. CGRP decreased the binding between HDAC5 and the Npas4 enhancer site and increased the binding between acetylated histone H3 and the Npas4 enhancer site. The pharmacological inhibition or knockdown of PKD attenuated the CGRP-mediated impairment of fear memory and the increased phosphorylation of HDAC5 and Npas4 expression. Our findings demonstrated that the CGRP-PKD pathway was associated with the histone H3 acetylation-Npas4 pathway. These results suggested a novel function for CGRP on fear memory, through epigenetic regulation.
format	article
author	Narumi Hashikawa-Hobara Shuta Mishima Chihiro Okujima Youdai Shitanishi Naoya Hashikawa
author_facet	Narumi Hashikawa-Hobara Shuta Mishima Chihiro Okujima Youdai Shitanishi Naoya Hashikawa
author_sort	Narumi Hashikawa-Hobara
title	Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice
title_short	Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice
title_full	Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice
title_fullStr	Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice
title_full_unstemmed	Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice
title_sort	npas4 impairs fear memory via phosphorylated hdac5 induced by cgrp administration in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fa12b5d6b2b149528e0bf685a1be2b22
work_keys_str_mv	AT narumihashikawahobara npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice AT shutamishima npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice AT chihirookujima npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice AT youdaishitanishi npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice AT naoyahashikawa npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice
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Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice

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