@article{oai:kumadai.repo.nii.ac.jp:00026797,
 author = {川原, 浩一 and 末延, 道太 and 吉田, 陽 and 古賀, 清弘 and Koga, Kiyohiro and 兵藤, 敦 and 大塚, 英起 and 國安, 明彦 and 玉巻, 伸章 and Tamamaki, Nobuaki and 杉本, 幸彦 and 中山, 仁 and Kawahara, Koichi and Suenobu, Michita and 吉田, 陽 and Yoshida, Akira and 古賀, 清弘 and Koga, Kiyohiro and Hyodo, Atsushi and Ohtsuka, Hideyuki and Kuniyasu, Akihiko and 玉巻, 伸章 and Tamamaki, Nobuaki and Sugimoto, Yukihiko and 中山, 仁 and Nakayama, Hitoshi},
 journal = {Neuroscience},
 month = {Apr},
 note = {application/pdf, 論文(Article), 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., http://www.sciencedirect.com/science/article/pii/S0306452212001029},
 pages = {243--260},
 title = {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},
 volume = {207},
 year = {2012},
 yomi = {コガ, キヨヒロ and タママキ, ノブアキ and ヨシダ, アキラ and コガ, キヨヒロ and タママキ, ノブアキ and ナカヤマ, ヒトシ}
}