A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse

Science. 2014 Oct 10;346(6206):237-41. doi: 10.1126/science.346.6206.237. Epub 2014 Oct 9.

Abstract

Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 ± 210 (mean ± SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / physiology*
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology
  • Gene Deletion
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Stem Cells / cytology
  • Neural Stem Cells / physiology*
  • Neurogenesis / genetics
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / physiology*
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / physiology*
  • Signal Transduction*
  • Stroke / pathology
  • Stroke / physiopathology*

Substances

  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Notch1 protein, mouse
  • Rbpj protein, mouse
  • Receptor, Notch1