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Intracerebral microinjection of interleukin-4/interleukin-13 reduces β-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice
http://hdl.handle.net/2298/26643
http://hdl.handle.net/2298/26643c065da01-5075-46a5-854e-5c0d191993b5
名前 / ファイル | ライセンス | アクション |
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lNeuroscience 2012 VOL207-5 .pdf (16.9 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-01-29 | |||||
タイトル | ||||||
タイトル | Intracerebral microinjection of interleukin-4/interleukin-13 reduces β-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題 | Alzheimer’s disease, β-amyloid, interleukin-4/interleukin-13, memory improvement, CD36, neprilysin | |||||
資源タイプ | ||||||
資源タイプ | journal article | |||||
著者 |
Kawahara, Koichi
× Kawahara, Koichi× Suenobu, Michita× 吉田, 陽× 古賀, 清弘× Hyodo, Atsushi× Ohtsuka, Hideyuki× Kuniyasu, Akihiko× 玉巻, 伸章× Sugimoto, Yukihiko× 中山, 仁 |
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別言語の著者 |
川原, 浩一
× 川原, 浩一× 末延, 道太× 吉田, 陽× 古賀, 清弘× 兵藤, 敦× 大塚, 英起× 國安, 明彦× 玉巻, 伸章× 杉本, 幸彦× 中山, 仁 |
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内容記述 | ||||||
内容記述 | We previously reported that the anti-inflammatory cytokine interleukin (IL)-4 induced selective clearance of oligomeric β-amyloid (Aβ1-42) in rat primary type 2 microglial cells. For the present study, we investigated whether IL-4 and IL-13 could activate microglial cells to induce Aβ clearance in vivo and improve cognitive deficits in APP23 mice, which are amyloid precursor protein transgenic mice. We administered an intracerebral microinjection of a mixture of IL-4 and IL-13 or of saline vehicle into one hemisphere of APP23 mice and their wild-type littermates, 4.5 and 9 months old, after which we evaluated the effects of these treatments on spatial learning and memory by Morris Water Maze test and on accumulated amounts of Aβ. The cytokine injection significantly improved memory deficits of 4.5-month-old APP23 mice, but did not do so in 9-month-old APP23 mice, even though similar Aβ reductions were observed in both age groups of APP23 mice in the ipsilateral neocortex. The cytokine injection improved memory impairment of 9-month-old WT mice in the probe trial. Immunohistochemical analysis of the 4.5-month-old APP23 mice revealed the presence of increased numbers of microglial cells at 2 days after the cytokine injection. In addition to induced CD36 expression in the activated microglia, increased expression of neprilysin, mainly in neurons, suggested that the cytokines improved the cognitive deficits via degradation and clearance of intra- and extraneuronal Aβ peptides, of buffer-extractable nonplaque form. Double immunostaining also revealed that most of the activated microglia had the M2-like phenotype. This unique mechanism of IL-4/IL-13-induced clearance of Aβ may provide an additional strategy to prevent and/or cure Alzheimer’s disease at early stage. |
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書誌情報 |
Neuroscience 巻 207, p. 243-260, 発行年 2012-04-05 |
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ISSN | ||||||
収録物識別子 | 03064522 | |||||
PubMed番号 | ||||||
関連タイプ | isVersionOf | |||||
関連識別子 | 22342341 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
関連識別子 | 10.1016/j.neuroscience.2012.01.049 | |||||
権利 | ||||||
権利情報 | © 2012 Elsevier Limited | |||||
フォーマット | ||||||
内容記述 | application/pdf | |||||
形態 | ||||||
16864170 bytes | ||||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
日本十進分類法 | ||||||
主題 | 493.7 | |||||
出版者 | ||||||
出版者 | Elsevier Limited | |||||
資源タイプ | ||||||
内容記述 | 論文(Article) | |||||
資源タイプ・ローカル | ||||||
雑誌掲載論文 | ||||||
資源タイプ・NII | ||||||
Journal Article | ||||||
資源タイプ・DCMI | ||||||
text | ||||||
資源タイプ・ローカル表示コード | ||||||
01 | ||||||
URL | ||||||
内容記述 | http://www.sciencedirect.com/science/article/pii/S0306452212001029 |