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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-03-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-86556-w |
| _version_ | 1818401169252286464 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T07:48:12Z |
| format | Article |
| id | doaj.art-fa12b5d6b2b149528e0bf685a1be2b22 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T07:48:12Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fa12b5d6b2b149528e0bf685a1be2b222022-12-21T23:10:50ZengNature PortfolioScientific Reports2045-23222021-03-0111111310.1038/s41598-021-86556-wNpas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in miceNarumi Hashikawa-Hobara0Shuta Mishima1Chihiro Okujima2Youdai Shitanishi3Naoya Hashikawa4Department of Life Science, Okayama University of ScienceDepartment of Life Science, Okayama University of ScienceDepartment of Life Science, Okayama University of ScienceDepartment of Life Science, Okayama University of ScienceDepartment of Life Science, Okayama University of ScienceAbstract 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.https://doi.org/10.1038/s41598-021-86556-w |
| spellingShingle | Narumi Hashikawa-Hobara Shuta Mishima Chihiro Okujima Youdai Shitanishi Naoya Hashikawa Npas4 impairs fear memory via phosphorylated HDAC5 induced by CGRP administration in mice Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-86556-w |
| work_keys_str_mv | AT narumihashikawahobara npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice AT shutamishima npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice AT chihirookujima npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice AT youdaishitanishi npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice AT naoyahashikawa npas4impairsfearmemoryviaphosphorylatedhdac5inducedbycgrpadministrationinmice |