title: Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke.
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.
authors: Research Institute, Shiga Medical Center, Moriyama 5-4-30, Shiga 524-8524, Japan.
authors: Takeshi
authors: T
authors: Marumo
authors: Yasushi
authors: Y
authors: Takagi
authors: Kazue
authors: K
authors: Muraki
authors: Nobuo
authors: N
authors: Hashimoto
authors: Susumu
authors: S
authors: Miyamoto
authors: Kenji
authors: K
authors: Tanigaki
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D001253:Astrocytes / Q000145:classification / Q000187:drug effects* / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus / Q000473:pathology; D049109:Cell Proliferation; D003593:Cytoplasm / Q000473:pathology; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D021381:Protein Transport / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D053829:Amyloid Precursor Protein Secretases; D051792:Basic Helix-Loop-Helix Proteins; D004151:Dipeptides; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D051880:Receptors, Notch; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C512773:Olig2 protein, mouse