Manipulation of Neural Precursors in situ Induction of Neurogenesis in the Neocortex of Adult Mice

Stem Cells The Promises and Pitfalls

“…(1) the role of neural stem cells during the developmental period and also during the complex tissue reorganization that is generally referred to as plasticity (Vaccarino et al 2001); (2) the intriguing idea that there exist neural stem cells in the neocortex that can be coaxed to become neurons (Magavi and Macklis 2001); (3) the idea that one population of proliferating cells in the adult brain, i.e. those in the dentate gyrus, may be involved in depression and stress and that neurogenesis in the dentate gyrus can be influenced by antidepressant therapies (Duman et al 2001).…”

“…A third population of stem cells has been suggested to reside in the substance of the brain itself in the form of cells with astrocyte-like properties (Laywell et al 2000). The existence of this population is part of the analysis of Magavi and Macklis (Magavi and Macklis 2001). How do these adult stem cell populations behave and how are they regulated?…”

“…In addition, one might speculate that the adult neural stem cells, rather than following an orderly sequence of events to produce specific products at specific times, respond instead to local environmental influences to produce an output appropriate for the conditions. The experiments of both Duman (Duman et al 2001) and Magavi and Macklis (Magavi and Macklis 2001) are oriented toward this possibility. However, at this stage we do not know if the various neural stem cell populations that exist in the adult animal have uniform or disparate potential (i.e.…”

“…Second, BrdU can label non-proliferating cells if they are synthesizing DNA. Thus, under some circumstances, for example the massive lesions exploited by Magavi and Macklis (Magavi and Macklis 2001), it is essential to determine if the observed BrdU incorporation is associated with: (1) DNA replication and cell proliferation or (2), with other conditions during which DNA is known to be synthesized in cells, i.e. DNA repair (Selden et al 1993), apoptosis (Katchanov et al 2001) or (3) with the development of tetraploidy (Yang et al 2001).…”

“…DNA repair (Selden et al 1993), apoptosis (Katchanov et al 2001) or (3) with the development of tetraploidy (Yang et al 2001). The experiments of Magavi and Macklis (Magavi and Macklis 2001) interpreted BrdU labeling as indication that "new neurons" have been made, but the pathology induced by the lesion could cause DNA synthesis to occur in "old neurons." For example, perhaps in a small percentage of the injured cells DNA repair is successful, and the neurons do not die.…”