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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
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Title: | 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 |
Authors: | Toda, Hiroyuki Browse this author | Boku, Shuken Browse this author →KAKEN DB | Nakagawa, Shin Browse this author →KAKEN DB | Inoue, Takeshi Browse this author →KAKEN DB | Kato, Akiko Browse this author | Takamura, Naoki Browse this author | Song, Ning Browse this author | Nibuya, Masashi Browse this author | Koyama, Tsukasa Browse this author →KAKEN DB | Kusumi, Ichiro Browse this author →KAKEN DB |
Issue Date: | 15-May-2014 |
Publisher: | Public Library of Science |
Journal Title: | PLOS One |
Volume: | 9 |
Issue: | 5 |
Start Page: | e97421 |
Publisher DOI: | 10.1371/journal.pone.0097421 |
PMID: | 24831231 |
Abstract: | 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. |
Rights: | http://creativecommons.org/licenses/by/3.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/57877 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 中川 伸
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