Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum

J Neurosci. 2006 Jun 14;26(24):6627-36. doi: 10.1523/JNEUROSCI.0149-06.2006.

Abstract

Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Count / methods
  • Cell Differentiation / physiology*
  • Cell Movement / physiology*
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology*
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Fluorescent Antibody Technique / methods
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Infarction, Middle Cerebral Artery
  • Lateral Ventricles / cytology*
  • Mice
  • Mice, Inbred ICR
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Neuropeptides / metabolism
  • Stem Cells / physiology*
  • Stroke / metabolism*
  • Stroke / physiopathology
  • Time Factors

Substances

  • Doublecortin Domain Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Green Fluorescent Proteins