WEKO3
アイテム
Regulation of Anxiety and Depression by Mitochondrial Translocator Protein-Mediated Steroidogenesis: the Role of Neurons
https://repo.qst.go.jp/records/80628
https://repo.qst.go.jp/records/80628c0d8850c-530a-4535-9c40-068e69a7aba9
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-10-02 | |||||
| タイトル | ||||||
| タイトル | Regulation of Anxiety and Depression by Mitochondrial Translocator Protein-Mediated Steroidogenesis: the Role of Neurons | |||||
| 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 | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Barron, Anna
× Barron, Anna× Higuchi, Makoto× Hattori, Satoko× Kito, Seiji× Suhara, Tetsuya× Ji, Bin× Barron, Anna× Makoto, Higuchi× Satoko, Hattori× Tetsuya, Suhara× Ji, Bin |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Pharmacological studies have implicated the translocator protein (TSPO) in the regulation of complex behaviors including anxiety and depression, effects thought to be mediated by increased synthesis of neuroactive steroid hormones. However, TSPO function in the brain remains to be corroborated in vivo via genetic studies. To address this, we developed global TSPO knockout (TSPO-KO) and neuronal TSPO transgenic (TSPO-Tg) mouse models to investigate TSPO function in the regulation of anxiety- and depression-related behaviors using elevated plus maze and forced swim test paradigms. Neuroactive steroid hormones were measured in the brain by mass spectrometry. In vivo TSPO ligand pharmacokinetics was investigated using competitive PET with 18F-FE-DAA1106. Genetic TSPO deficiency increased anxiety-related behavior and impaired brain steroidogenesis but did not affect depressive behaviors. Using the TSPO-KO model, we then demonstrated the specificity of Ac-5216, also known as XBD-173 or Emapunil, as an anxiolytic targeting TSPO at doses optimized by competitive PET for high cortical occupancy. Neuronal TSPO overexpression decreased depressive behaviors, an effect that was dependent on steroidogenesis, and partially reversed anxiogenic behavior in TSPO-KOmice. These findings demonstrate that TSPO is critical for brain steroidogenesis and modulates anxiety- and depression-related behaviors. However, we demonstrate that key differences in the contribution of neuronal TSPO to the modulation of these complex behaviors, illustrating the tissue- and cell-specific importance of TSPO. The TSPO-KO and TSPO-Tg mice provide the tools and rationale for the development of therapeutic approaches targeting TSPO in the brain for treatment of neuropsychiatric conditions. |
|||||
| 書誌情報 |
Molecular Neurobiology 巻 58, 号 2, p. 550-563, 発行日 2020-09 |
|||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0893-7648 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 32989676 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1007/s12035-020-02136-5 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://link.springer.com/article/10.1007/s12035-020-02136-5 | |||||
