Abstract

Dear Editor,
In this issue of MSM, in his letter entitled “Consideration of adult neurogenesis from physiological and patho-physiological aspects”, Dr Toshiyuki Saito comments on the mechanisms and functionality of neurogenesis in the adult brain. Dr Saito points out to some of the mechanisms and functionality of adult neural stem cells (NSCs) that remain to be fully understood, to the complexity of the mechanisms underlying neurogenesis, and their consequence to the understanding of the physio-pathology of the central nervous system (CNS) and to cellular therapy.
With the confirmation that neurogenesis occurs throughout adulthood in discrete areas of the adult brain, and that NSCs reside in the adult CNS [1], the promise of this field of research lies in the new opportunities for the treatment of yet incurable brain diseases and injuries, and to our understanding of developmental biology and of the physio-pathology of the adult CNS.
Since the seminal work of Altman and Das in the early 60s, and more so since the 80s and 90s, significant advances have been made in the field of adult neurogenesis and NSCs. Yet, fundamental questions remain to be addressed with regard to the identity, origin, potential, function, and therapeutic potential of these cells in the CNS. Molecular markers and mechanisms underlying NSCs maintenance, growth and fate determination remain to be fully characterized. Though an astroglial origin has gain significant momentum, the origin and identity of NSCs is still the subject of debates. Reports that adult NSCs would have a broader potential have also fueled their shares of controversies. Adult neurogenesis has been involved in learning and memory, depression, and in various pathologies of the CNS, such as neurological diseases and injuries. However, the function(s) of newly generated neuronal cells in the physio-pathology of the CNS remains to be determined, and adult NSCs have yet to be brought to therapy [2].
The complexity of the phenomenon’s underlying the involvement of neurogenesis in vivo, and the heterogeneity of the currently established protocols to isolate neural progenitor and stem cells in vitro are among the factors contributing to the difficulties to assess the role and function of neurogenesis to the physio-pathology of the CNS, and to its therapeutic development.
Recent studies have tackled these issues. Homogenous population of neural progenitor/stem cells have been isolated and characterized in vitro, using cell surface markers such as the protein CD133 [3], the carbohydrate moiety LeX [4], syndecan-1, Notch-1 and integrin-beta1 [5], by promoter-targeted selection [6,7], by negative selection [8], and by “side-population” analysis [9]. In vivo, recent studies have identified differences between newly generated neuronal cells and mature neurons. Newly generated neurons express unique mechanisms, such as T-type Ca[sup]2+[/sup] channels that generate isolated Ca[sup]2+[/sup] spikes and boost fast Na[sup]+[/sup] action potentials, facilitating synaptic plasticity [10].
These studies aiming at identifying specifics molecular and cellular markers and pathways of neural progenitor/stem cells will contribute to the development of therapeutic drugs and cell therapeutic techniques [11], hence to bring NSC research closer to therapy.

Sincerely
Philippe Taupin
National Neuroscience Institute,
National University of Singapore,
11 Jalan Tan Tock Seng, Singapore 308433, Singapore,
e-mail:[email protected]

References:
1.Taupin P, Gage FH: Adult neurogenesis and neural stem cells of the central nervous system in mammals. J Neurosci Res, 2002; 69: 745–49
2.Taupin P: Adult neurogenesis in the mammalian central nervous system: functionality and potential clinical interest. Med Sci Monit, 2005; 11(7): RA247–RA252
3.Uchida N, Buck DW, He D et al: Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA, 2000; 97: 14720–25
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6.Wang S, Roy NS, Benraiss A, Goldman SA: Promoter-based isolation and fluorescence-activated sorting of mitotic neuronal progenitor cells from the adult mammalian ependymal/subependymal zone. Dev Neurosci, 2000; 22: 167–76
7.Roy NS, Benraiss A, Wang S et al: Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone. J Neurosci Res, 2000; 59: 321–31
8.Rietze RL, Valcanis H, Brooker GF et al: Purification of a pluripotent neural stem cell from the adult mouse brain. Nature, 2001; 412: 736–39
9.Kim M, Morshead CM: Distinct populations of forebrain neural stem and progenitor cells can be isolated using side-population analysis. J Neurosci, 2003; 23, 10703–9
10.Schmidt-Hieber C, Jonas P, Bischofberger J: Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature, 2004; 429: 184–87
11.Tamaki S, Eckert K, He D et al: Engraftment of sorted/expanded human central nervous system stem cells from fetal brain. J Neurosci Res, 2002; 69: 976–86

Keywords: Central Nervous System - injuries, Nervous System Diseases - therapy, Stem Cells - cytology, Wounds and Injuries - therapy