Bcl-2 enhances neurogenesis and inhibits apoptosis of newborn neurons in adult rat brain following a transient middle cerebral artery occlusion.
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.
Zhang
Rong
R
State Key Laboratory of Medical Neurobiology, Institute for Biomedical Sciences, Shanghai Medical College of Fudan University, 138, Yi-Xue-Yuan Road, Shanghai 200032, P. R. China.
Xue
Yu-Yu
YY
Lu
Shi-Duo
SD
Wang
Yao
Y
Zhang
Ling-Mei
LM
Huang
Ya-Lin
YL
Signore
Armando P
AP
Chen
Jun
J
Sun
Feng-Yan
FY
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D019610:Cytoprotection / Q000235:genetics; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D005822:Genetic Vectors / Q000235:genetics; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D014162:Transfection; D016896:Treatment Outcome; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; C462941:beta3 tubulin, mouse; D053148:Caspase 3