Discovery of Neural Stem Cells

Fifty years ago it was dogma that neurogenesis ceased after birth in the CNS of mammals. Then, in the early 1960s, 3H-thymidine labeling studies in adult rats revealed cells actively synthesizing DNA in the hippocampus, leading to the hypothesis that maintenance regeneration is taking place in this region of the brain (Messier et al., 1958; Smart, 1961; Altman, 1962, 1963). The idea of maintenance regeneration in the CNS of any vertebrate was not accepted, however, until Nottebohm and colleagues showed in the 1980s that in male canaries there is a tremendous increase each spring in the number of neurons in their vocal control brain nuclei. These neurons are recruited into song-learning circuits and die when the mating season is over (Goldman and Nottebohm, 1983; Paton and Nottebohm, 1984). Thus, it was shown conclusively that there is neuron turnover and replacement in the adult canary brain, but the dogma of "no new neurons" remained in force for the mammalian brain.

This dogma was shattered for good in the 1990s by the discovery of neural stem cells (NSCs) in different parts of the mammalian brain. figure 5.12 illustrates how NSCs (and stem cells in general) are identified.

BrdU

in vitro

BrdU

in vitro

NSE BrdU ├čTUIII and/or + NeuN GFP GABA sP

GFP or LacZ Transgene

Nestin

Nrp-1

PNAto

HSAto

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