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Imaging of Peripheral Benzodiazepine Receptor Expression as Biomarkers of Detrimental Versus Beneficial Glial Responses in Mouse Models of Alzheimer's and Other CNS Pathologies
https://repo.qst.go.jp/records/45393
https://repo.qst.go.jp/records/453934ef6fe2b-0498-47d4-a6b9-b8d712798f9e
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2009-01-08 | |||||
| タイトル | ||||||
| タイトル | Imaging of Peripheral Benzodiazepine Receptor Expression as Biomarkers of Detrimental Versus Beneficial Glial Responses in Mouse Models of Alzheimer's and Other CNS Pathologies | |||||
| 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 |
Ki, Hin
× Ki, Hin× Maeda, Jun× Sawada, Makoto× Ono, Maiko× Okauchi, Takashi× Inaji, Motoki× Zhang, Ming-Rong× Suzuki, Kazutoshi× Andou, Kiyoshi× Staufenbiel, Matthias× Q., Trojanowski John× M.-Y., Lee Virginia× Higuchi, Makoto× Suhara, Tetsuya× 季 斌× 前田 純× 澤田 誠× 小野 麻衣子× 岡内 隆× 稲次 基希× 張 明栄× 鈴木 和年× 安東 潔× 樋口 真人× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | We demonstrate the significance of peripheral benzodiazepine receptor (PBR) imaging in living mouse models of Alzheimer's disease(AD) as biomarkers and functional signatures of glial activation. By radiochemically and immunohistochemically analyzing murinemodels of the two pathological hallmarks of AD, we found that AD-like Abeta deposition is concurrent with astrocyte-dominant PBRexpression, in striking contrast with nonastroglial PBR upregulation in accumulations of AD-like phosphorylated tau. Because tauinduced massive neuronal loss was distinct from the marginal neurodegeneration associated with Abeta plaques in these models, cellular localization of PBR reflected deleterious and beneficial glial reactions to tau versus Abeta pathologies, respectively. This notion was subsequently examined in models of various non-AD neuropathologies, revealing the following reactive glial dynamics underlying differential PBR upregulation: (1) PBR(-) astrogliosis uncoupled with microgliosis or coupled with PBR(+) microgliosis associated with irreversible neuronal insults; and (2) PBR(+) astrogliosis coupled with PBR(- or +-) microgliosis associated with minimal or reversible neuronal toxicity. Intracranial transplantation of microglia also indicated that nontoxic microglia drives astroglial PBR expression. Moreover, levels of glial cell line-derived neurotrophic factor (GDNF) in astrocytes were correlated with astroglial PBR, except for increased GDNF in PBR(-) astrocytes in the model of AD-like tau pathology, thereby suggesting that PBR upregulation in astrocytes is an indicator of neurotrophic support. Together, PBR expressions in astrocytes and microglia reflect beneficial and deleterious glial reactions, respectively, in diverse neurodegenerative disorders including AD, pointing to new applications of PBR imaging for monitoring the impact of gliosis on the pathogenesis and treatment of AD. |
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| 書誌情報 |
The Journal of Neuroscience 巻 28, 号 47, p. 12255-12267, 発行日 2008-11 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0270-6474 | |||||
