| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
The role of glucocorticoid receptors in the induction and prevention of hippocampal abnormalities in an animal model of posttraumatic stress disorder |
|
言語 |
en |
| 作成者 |
Araki, Motoaki
Fuchikami, Manabu
Omura, Jun
Miyagi, Tatsuhiro
Nagashima, Nobuyuki
Okamoto, Yasumasa
Morinobu , Shigeru
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
権利情報 |
This is a post-peer-review, pre-copyedit version of an article published in Psychopharmacology. The final authenticated version is available online at: https://doi.org/10.1007/s00213-020-05523-x |
| 権利情報 |
|
|
権利情報 |
This is not the published version. Please cite only the published version. この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Animal model |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Posttraumatic stress disorder (PTSD) |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Glucocorticoid receptor (GR) |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
GR antagonist |
| 内容記述 |
|
|
内容記述 |
Rationale: Since the precise mechanisms of posttraumatic stress disorder (PTSD) remain unknown, effective treatment interventions have not yet been established. Numerous clinical studies have led to the hypothesis that elevated glucocorticoid levels in response to extreme stress might trigger a pathophysiological cascade which consequently leads to functional and morphological changes in the hippocampus. Objectives: To elucidate the pathophysiology of PTSD, we examined the alteration of hippocampal gene expression through the glucocorticoid receptor (GR) in the single prolonged stress (SPS) paradigm, a rat model of PTSD. Methods: We measured nuclear GRs by western blot, and the binding of GR to the promoter of Bcl-2 and Bax genes by chromatin immunoprecipitation-qPCR as well as the expression of these 2 genes by RT-PCR in the hippocampus of SPS rats. In addition, we examined the preventive effects of a GR antagonist on SPS-induced molecular, morphological, and behavioral alterations (hippocampal gene expression of Bcl-2 and Bax, hippocampal apoptosis using TUNEL staining, impaired fear memory extinction (FME) using the contextual fear conditioning paradigm). Results: Exposure to SPS increased nuclear GR expression and GR binding to Bcl-2 gene, and decreased Bcl-2 mRNA expression. Administration of GR antagonist immediately after SPS prevented activation of the glucocorticoid cascade, hippocampal apoptosis, and impairment FME in SPS rats. Conclusion: The activation of GRs in response to severe stress may trigger the pathophysiological cascade leading to impaired FME and hippocampal apoptosis. In contrast, administration of GR antagonist could be useful for preventing the development of PTSD. |
|
言語 |
en |
| 内容記述 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (a grant-in aid for Scientific Research, C) Grant Number JP18K07562, and Takeda Science Foundation. |
| 出版者 |
|
|
出版者 |
Springer |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
AO |
|
出版タイプResource |
http://purl.org/coar/version/c_b1a7d7d4d402bcce |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1007/s00213-020-05523-x |
| 関連情報 |
|
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
32333135 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1007/s00213-020-05523-x |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0033-3158 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1432-2072 |
| 開始ページ |
|
|
開始ページ |
2125 |
| 書誌情報 |
Psychopharmacology
Psychopharmacology
巻 237,
号 7,
p. 2125-2137,
発行日 2020-07
|
| 旧ID |
50463 |
| 備考 |
Post-print version/PDF may be used in an institutional repository after an embargo period of 12 months. |
Psychopharmacology_237_2125.pdf (1.1 MB)
