論文

査読有り 国際誌
2021年3月26日

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

Scientific reports
  • Narumi Hashikawa-Hobara
  • ,
  • Shuta Mishima
  • ,
  • Chihiro Okujima
  • ,
  • Youdai Shitanishi
  • ,
  • Naoya Hashikawa

11
1
開始ページ
7006
終了ページ
7006
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-021-86556-w

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.

リンク情報
DOI
https://doi.org/10.1038/s41598-021-86556-w
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33772088
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997869
ID情報
  • DOI : 10.1038/s41598-021-86556-w
  • PubMed ID : 33772088
  • PubMed Central 記事ID : PMC7997869

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