Zhang Rong, Xue Yu-Yu, Lu Shi-Duo, Wang Yao, Zhang Ling-Mei, Huang Ya-Lin, Signore Armando P, Chen Jun, Sun Feng-Yan
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.
Neurobiol Dis. 2006 Nov;24(2):345-56. doi: 10.1016/j.nbd.2006.07.012. Epub 2006 Sep 25.
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.
为了确定Bcl-2是否会影响成体神经发生并防止新生神经元凋亡,我们在大脑中动脉闭塞(MCAO)30分钟后,立即将表达Bcl-2的质粒注入大鼠脑侧脑室。我们发现,在MCAO后1至4周,Bcl-2增加了同侧纹状体中的神经祖细胞(BrdU+-DCX+)、同侧纹状体和额叶皮质中的新生未成熟神经元(BrdU+-Tuj-1+)以及新生成熟神经元(BrdU+-MAP-2+)。Bcl-2的过表达促进了同侧纹状体中新生神经元向GABA能和胆碱能神经元的发育。此外,通过Tuj-1和活化的caspase-3双重染色(Tuj-1+-Casp+)确定,Bcl-2显著降低了新生神经元的凋亡。这些结果表明,成年大鼠脑中Bcl-2的过表达增强了新生神经元的神经发生和存活。增加神经发生并防止新生神经元死亡可能是有助于中风后成年大脑修复的一种策略。