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2015年01月22日

Evidence for oligodendrocyte dedifferentiation and subsequent formation of astrocytes after acute cortical injuries

日 時 2015年01月22日(木) 13:00 より 14:00 まで
講演者 Frank Kirchhoff 教授
講演者所属 The Department of Molecular Physiology, Institute of Physiology, University of Saarland
お問い合わせ先 分子神経生理 池中一裕 ikenaka@nips.ac.jp (内線:5245)
要旨

この度、新学術で招聘中のFrank Kirchhoff 教授、David Rowitch 教授を招待し 下記の通り、所長招聘セミナーを開催いたします。
皆様多数ご来聴ください。
セミナーは英語で行われます。

Acute brain injuries lead to glial scar formation. Quiescent mature astrocytes get activated and proliferate in response to brain injuries. In recent years, studies suggested that a population of oligodendrocyte precursor cells (OPCs) could generate astrocytes after acute cortical injuries, though the contribution of OPCs to astrogliosis varied with animal and injury models. Here, we report that not only OPCs but also oligodendrocytes take part in the astrogliosis. Using NG2-CreERT2 knock-in mice we selectively induced a genetic label into OPCs and their putative progeny. Subsequently, we observed that acute brain injuries induced more astrocytes with this genetic marker when the pool of labeled oligodendrocytes was increased. Immunohistochemical and in vivo two-photon laser scanning microscopy analyses showed that a subpopulation of activated oligodendrocytes displayed astroglial transgenic GFAP promoter activity after a variety of acute cortical injuries. We termed these cells "OA cells" because of their oligodendro- and astroglial properties. Targeting exclusively OA cells with a split-Cre mouse model showed a broader but glia-restricted differentiation potential of OA cells differentiating to astrocytes, OPCs and oligodendrocytes. The differentiation of OA cells appeared to be dependent on local cues: OA cell-derived astrocytes were more frequently found in the superficial cortical layers I-III, while OA cell-derived oligodendrocytes were preferentially located in layers V-VI near the corpus callosum. Using qRT-PCR, we found higher expression levels of glial differentiation factors such as bone morphogenetic protein 4 (BMP4), interleukin 6 (IL-6), ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) at the lesion site. In addition, we could promote the formation of OA cells by injection of IL-6, while LIF appeared to inhibit the dedifferentiation of oligodendrocyte. In conclusion, our data suggest that not only OPCs but rather the whole oligodendroglial lineage including oligodendrocytes has the ability to generate astrocytes after acute cortical injuries dependent on local cues.