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Ligand of translocator protein stimulates neurosteroid synthesis and reverses pathology in a mouse model of Alzheimer`s disease
https://repo.qst.go.jp/records/71615
https://repo.qst.go.jp/records/71615ebf52dc5-b21a-4572-84e6-373bacdbadc0
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-04-20 | |||||
| タイトル | ||||||
| タイトル | Ligand of translocator protein stimulates neurosteroid synthesis and reverses pathology in a mouse model of Alzheimer`s disease | |||||
| 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_c94f | |||||
| 資源タイプ | conference object | |||||
| 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× M., GARCIA-SEGURA L.× CARUSO, D.× JAYARAMAN, A.× LEE, J.-W.× C., MELCANGI R.× Ji, Bin× Higuchi, Makoto× Ｂａｒｒｏｎ Ａｎｎａ× 季 斌× 樋口 真人 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Translocator protein (TSPO) is a multi-functional mitochondrial transmembrane protein primarily localised in steroid-producing tissues, including the brain. TSPO ligands elicit pleiotropic neuroprotective and cognitive benefits mechanistically linked to the regulation of steroid synthesis and consequently represent emerging treatment strategies for several neurodegenerative conditions. To investigate the potential of TSPO as a therapeutic target for Alzheimer's disease (AD), the current study assessed the effects of the TSPO ligand Ro5-4864 on the development of neuropathology in the triple transgenic mouse model (3xTgAD). In 3xTgAD mice, the effects of the TSPO ligand on neurosteroidogenesis and AD-related neuropathology including β-amyloid accumulation, gliosis and behavioral impairment were examined under both early intervention (7 month-old young-adult male mice with low pathology) and treatment (24 month-old, aged male mice with advanced neuropathology) conditions. Ro5-4864 treatment not only effectively attenuated development of neuropathology and behavioral impairment in young adult mice, but also reversed these indices in aged 3xTgAD mice. In the young-adult mice, these benefits were associated with increased brain levels of the potent neuroactive steroid hormones, testosterone and progesterone. Because TSPO ligands can differentially modulate TSPO activities, we also compared the independent and combined effects of Ro5-4864 with PK-11195 (a non-benzodiazepine TSPO ligand) on endogenous β-amyloid in wild type mice, finding an additive anti-amyloidogenic effect of combined treatment. To determine the contribution of increased neurosteroid synthesis to the β-amyloid reducing effects of Ro5-4864 in the wild type mice, we co-administered Ro5-4864 with a neurosteroidogenesis inhibitor, aminoglutethimide. We next compared the effect of old (Ro5-4864, PK-11195) and new-generation TSPO ligands (AC-5216, DAA-1106) on endogenous β-amyloid in wild type mice. New generation TSPO ligands such as AC-5216 have already undergone significant clinical development for treatment of anxiety disorders and depression, however our findings suggest these ligands may also have a therapeutic potential for the treatment of Alzheimer`s. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | The Society for Neuroscience meeting 2013 | |||||
| 発表年月日 | ||||||
| 日付 | 2013-11-11 | |||||
| 日付タイプ | Issued | |||||
