Bcl-2 enhances neurogenesis and inhibits apoptosis of newborn neurons in adult rat brain following a transient middle cerebral artery occlusion

Neurobiol Dis. 2006 Nov;24(2):345-56. doi: 10.1016/j.nbd.2006.07.012. Epub 2006 Sep 25.

Abstract

To determine whether Bcl-2 could influence adult neurogenesis and prevent apoptosis of newborn neurons, we injected Bcl-2 expressing plasmid into the lateral ventricle of rat brain immediately following a 30-min occlusion of the middle cerebral artery (MCAO). We found that Bcl-2 increased neural progenitor cells (BrdU+-DCX+) in the ipsilateral striatum, newborn immature neurons (BrdU+-Tuj-1+) and newborn mature neurons (BrdU+-MAP-2+) in the ipsilateral striatum and frontal cortex at 1 to 4 weeks following MCAO. Bcl-2 overexpression promoted development of newborn neurons into GABAergic and cholinergic neurons in the ipsilateral striatum. Moreover, Bcl-2 significantly decreased the apoptosis of newborn neurons, determined by double staining of Tuj-1 and activated caspase-3 (Tuj-1+-Casp+). These results indicate that overexpression of Bcl-2 in adult rat brain enhances neurogenesis and survival of newborn neurons. Increasing neurogenesis and preventing the death of newborn neuron may be a strategy to aid in the repair of adult brain after stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Caspase 3 / metabolism
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Cytoprotection / genetics
  • Disease Models, Animal
  • Doublecortin Protein
  • Genetic Vectors / genetics
  • Infarction, Middle Cerebral Artery / metabolism*
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / therapy
  • Interneurons / cytology
  • Interneurons / metabolism
  • Male
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / physiopathology
  • Nerve Degeneration / prevention & control
  • Neurons / cytology
  • Neurons / metabolism*
  • Prosencephalon / cytology
  • Prosencephalon / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stroke / metabolism
  • Stroke / physiopathology
  • Stroke / therapy
  • Transfection
  • Treatment Outcome
  • Tubulin / metabolism
  • Up-Regulation / genetics

Substances

  • Dcx protein, mouse
  • Dcx protein, rat
  • Doublecortin Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Tubulin
  • beta3 tubulin, mouse
  • Caspase 3