Maternal Separation Enhances Conditioned Fear and Decreases the mRNA Levels of the Neurotensin Receptor 1 Gene with Hypermethylation of This Gene in the Rat Amygdala

Toda, Hiroyuki; Boku, Shuken; Nakagawa, Shin; Inoue, Takeshi; Kato, Akiko; Takamura, Naoki; Song, Ning; Nibuya, Masashi; Koyama, Tsukasa; Kusumi, Ichiro

Maternal Separation Enhances Conditioned Fear and Decreases the mRNA Levels of the Neurotensin Receptor 1 Gene with Hypermethylation of This Gene in the Rat Amygdala

Toda, Hiroyuki; Boku, Shuken; Nakagawa, Shin et al.

PLOS One, 2014, 9(5), e97421

Permalink : https://hdl.handle.net/2115/57877

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アクセス権	open access
URI	https://hdl.handle.net/2115/57877
タイトル	Maternal Separation Enhances Conditioned Fear and Decreases the mRNA Levels of the Neurotensin Receptor 1 Gene with Hypermethylation of This Gene in the Rat Amygdala
著者	Toda, Hiroyuki ; Boku, Shuken ; Nakagawa, Shin ; Inoue, Takeshi ; Kato, Akiko ; Takamura, Naoki ; Song, Ning ; Nibuya, Masashi ; Koyama, Tsukasa ; Kusumi, Ichiro
著者名 Toda, Hiroyuki
e-Rad_Researcher 60455665 著者名 Boku, Shuken
e-Rad_Researcher 60360905 著者名 Nakagawa, Shin
e-Rad_Researcher 70250438 著者名 Inoue, Takeshi
著者名 Kato, Akiko
著者名 Takamura, Naoki
著者名 Song, Ning
著者名 Nibuya, Masashi
e-Rad_Researcher 10113557 著者名 Koyama, Tsukasa
e-Rad_Researcher 30250426 著者名 Kusumi, Ichiro
言語	英語
発行日	2014-05-15
出版者	Public Library of Science
収録物名	PLOS One
巻(号)	9(5)
ページ	e97421
抄録	Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such "programmed" effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS) is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS). The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR) 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1932-6203
関連情報	PMID 24831231
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1371/journal.pone.0097421