Department of Neurobiology and Institute of Stem Cell Research, Institutes for Biomedical Science, Shanghai Medical College, Fudan University; State Key Laboratory of Medical Neurobiology of Fudan University, Shanghai 200032, China

Abstract 

Objective It has been reported that B-cell lymphoma 2 (Bcl-2) enhances neurogenesis as well as supporting axonal growth after injury. In the present study, we investigated whether Bcl-2 overexpression plays a role in the
formation of newborn striatonigral projection neurons in the adult rat brain after transient middle cerebral artery occlusion (MCAO). MethodsWe infused human Bcl-2-expressing plasmid (pBcl-2) into the lateral ventricle immediately after 30 min of MCAO, injected 5’-bromodeoxyuridine (BrdU) intraperitoneally to label proliferative cells, and microinjected fluorogold (FG) into the substantia nigra at 11 weeks of reperfusion followed by multiple immunostaining of striatonigral
projection neurons at 12 weeks. Results We found that pBcl-2 treatment significantly increased the number of newborn neurons (BrdU+-NeuN+) in the striatum ipsilateral to the MCAO. We further detected newborn striatonigral projection neurons (BrdU+-FG+-NeuN+) in the ipsilateral striatum at 12 weeks. More interestingly, the number of newborn striatonigral projection neurons (BrdU+-FG+) was significantly increased by pBcl-2 treatment compared to that by pEGFP, a control plasmid. Conclusion Taken together, we found that Bcl-2 overexpression in the brain enhanced the generation of newborn striatonigral projection neurons. This provides a potential strategy for promoting the reestablishment of neural networks and brain repair after ischemic injury.

Keywords

cerebral ischemia; Bcl-2; striatonigral projection neuron; neurogenesis; brain repair

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