Is integration and survival of newborn neurons the bottleneck for effective neural repair by endogenous neural precursor cells?

Ann M. Turnley, Harleen S. Basrai, Kimberly J. Christie

After two decades of research the existence of adult neural precursor cells and the phenomenon of adult neurogenesis is well established. However, there has been little or no effective harnessing of these endogenous cells to promote functional neuronal replacement following neural injury or disease. Neural precursor cells can respond to neural damage by proliferating, migrating to the site of injury, and differentiating into neuronal or glial lineages. However, after a month or so, very few or no newborn neurons can be detected, suggesting that even though neuroblasts are generated, they generally fail to survive as mature neurons and contribute to the local circuitry. Is this lack of survival and integration one of the major bottlenecks that inhibits effective neuronal replacement and subsequent repair of the nervous system following injury or disease? In this perspective article the possibility that this bottleneck can be targeted to enhance the integration and subsequent survival of newborn neurons will be explored and will suggest some possible mechanisms that may need to be modulated for this to occur.