Lengthening the G1 phase of neural progenitor cells is concurrent with an increase of symmetric neuron generating division after stroke

Abstract

The proportion of neural progenitors that remain in (P fraction) and exit from (Q fraction) the cell cycle determines the degree of neurogenesis. Using S-phase labeling with 5-bromo-2′-deoxyuridine and a double nucleoside analog-labeling scheme, we measured the cell-cycle kinetics of neural progenitors and estimated the proportion of P and Q fractions in the subventricular zone (SVZ) of adult rats subjected to stroke. Stroke increased SVZ cell proliferation, starting 2 days, reaching a maximum 4 and 7 days after stroke. The cell-cycle length (TC) of SVZ cells changed dynamically over a period of 2 to 14 days after stroke, with the shortest length of 11 h at 2 days after stroke. The reduction of the TC resulted from a decrease of the G1 phase because the G2, M, and S phases were unchanged. In addition, during this period, reduction of the G1 phase was concomitant with an increase in the P fraction, whereas an augmentation of the Q fraction was associated with lengthening of the G1 phase. Furthermore, approximately 90% of cells that exited the cell cycle were neurons and the population of a pair of dividing daughter cells with a neuronal marker increased from 9% at 2 days to 26% at 14 days after stroke. These data suggest that stroke triggers early expansion of the progenitor pool via shortening the cell-cycle length and retaining daughter cells within the cell cycle, and the lengthening of G1 leads to daughter cells exiting the cell cycle and differentiating into neurons. © 2008 ISCBFM All rights reserved.