RRC ID 20976
著者 Marumo T, Takagi Y, Muraki K, Hashimoto N, Miyamoto S, Tanigaki K.
タイトル Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke.
ジャーナル Neurosci Res
Abstract Treatment with DAPT, an inhibitor of the Notch-activating enzyme, γ-secretase is known to reduce damage to ischemic brain. However, the molecular mechanisms supporting this therapeutic effect are not fully understood. Here we demonstrated that Notch/RBP-J signaling is activated in NG2(+) glial progenitors and reactive astrocytes such as GFAP(+) cells, Nestin(+) cells and RC2(+) cells, using Notch/RBP-J signaling reporter mice. 3-day DAPT treatment reduced the number of reactive astrocytes but not NG2(+) glial progenitors. BrdU labeling experiments have shown that this reduction was due to decreased proliferation of reactive astrocytes. DAPT inhibited nuclear-translocation of Olig2, which is indispensable for proliferation and differentiation of reactive astrocytes. These findings suggest that Notch signaling might promote proliferation and differentiation of reactive astrocytes through the regulation of nucleo-cytoplasmic translocation of Olig2.
巻・号 75(3)
ページ 204-9
公開日 2013-3-1
DOI 10.1016/j.neures.2013.01.006
PII S0168-0102(13)00008-4
PMID 23396245
MeSH Amyloid Precursor Protein Secretases / antagonists & inhibitors Animals Astrocytes / classification Astrocytes / drug effects* Astrocytes / pathology Basic Helix-Loop-Helix Transcription Factors / biosynthesis Basic Helix-Loop-Helix Transcription Factors / metabolism* Cell Differentiation / physiology Cell Nucleus / pathology Cell Proliferation Cytoplasm / pathology Dipeptides / administration & dosage Dipeptides / pharmacology Disease Models, Animal Mice Mice, Transgenic Nerve Tissue Proteins / biosynthesis Nerve Tissue Proteins / metabolism* Neurogenesis / physiology* Neuroglia / metabolism* Oligodendrocyte Transcription Factor 2 Protein Transport / physiology Receptors, Notch / physiology* Signal Transduction / physiology* Stroke / drug therapy Stroke / metabolism* Stroke / pathology
IF 2.645
引用数 24
WOS 分野 NEUROSCIENCES
リソース情報
遺伝子材料 RBP-J-Venus (RDB08964)
実験動物マウス RBRC03783