Proliferating neural precursor cells as first step toward neuroregeneration in Huntington's disease?

Editor's Note: These short reviews of a recent paper in the Journal, written exclusively by graduate students or postdoctoral fellows, are intended to mimic the journal clubs that exist in your own departments or institutions. For more information on the format and purpose of the Journal Club, please see Review of Batista et al. Endogenous neural stem cells (NSCs) within the adult mammalian forebrain have been demonstrated to undergo enhanced cell proliferation and differentiation in response to neurodegenerative disease. Increased proliferation of cells in the subependyma (SE) was also noted in the human Huntington's disease (HD) brain. A recent article in The Journal of Neuro-science (Batista et al., 2006) demonstrated non-cell-autonomous-induced increase in NSC numbers along with altered migration of neural progenitors into the stri-atum in the R6/2 mouse model of HD. To measure the number of NSCs in vivo, the authors used the in vitro neuro-sphere assay and determined that the total number of spheres forming from cells isolated from the SE was progressively increased in symptomatic R6/2 animals relative to wild-type (wt), in an age-dependent manner [Batista et al. Examining retention of bromodeoxyuridine (BrdU) labeling over 30 d confirmed the specific increase of NSC numbers in symptomatic R6/2 mice. Additional support for BrdUϩ cells in the SE as being NSCs came from the observation that the vast majority of these cells expressed both nestin and GFAP, reflecting the multi-potent nature of NSCs [Batista et al. (2006), their Fig. 2logical analysis of cells in the SE by electron microscopy also demonstrated a specific increase in the proportion of type B cells, which correspond to putative stem cells, in R6/2 animals relative to controls [Batista et al. Self-renewal capacity of NSCs from symptomatic R6/2 mice was also increased [Batista et al. (2006), their Fig. 4 A cultured from presymptomatic R6/2 mice gave rise to similar numbers of neuro-spheres formed as did wt mice, and did not display increased expansion capacity [Batista et al.tiation of the self-renewal ability of sub-ependymal NSCs from symptomatic R6/2 mice may be induced by factors in the intact brain during symptom onset. Despite increased clonal expansion, the multipo-tentiality of NSCs is not different between R6/2 and wt, because comparable proportions of neurons, astrocytes, and oligo-dendrocytes are formed from NSCs of either genotype. Furthermore, the authors found no significant difference in the proliferation of subependymal progenitors from R6/2 mice relative to wt, using either cumulative BrdU labeling …