Progenitors in the adult cerebral cortex: Cell cycle properties and regulation by physiological stimuli and injury

Abstract

The adult brain parenchyma contains a widespread population of progenitors generating different cells of the oligodendrocyte lineage such as NG2+ cells and some mature oligodendrocytes. However, it is still largely unknown how proliferation and lineage decisions of these progenitors are regulated. Here, we first characterized the cell cycle length, proliferative fraction, and progeny of dividing cells in the adult cerebral cortex and then compared these proliferation characteristics after two distinct stimuli, invasive acute brain injury and increased physiological activity by voluntary physical exercise. Our data show that adult parenchymal progenitors have a very long cell cycle due to an extended G1 phase, many of them can divide at least twice and only a limited proportion of the progeny differentiates into mature oligodendrocytes. After stab wound injury, however, many of these progenitors re-enter the cell cycle very fast, suggesting that the normally long G1 phase is subject to regulation and can be abruptly shortened. In striking contrast, voluntary physical exercise shows the opposite effect with increased exit of the cell cycle followed by an enhanced and fast differentiation into mature oligodendrocytes. Taken together, our data demonstrate that the endogenous population of adult brain parenchymal progenitors is subject to profound modulation by environmental stimuli in both directions, either faster proliferation or faster differentiation.

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

“…However, only about 10–20% of astrocytes divide in this injury model (Bardehle et al, 2013; Simon et al, 2011), suggesting that only some may reach levels of expression sufficient to complete the cell cycle. Indeed, some genes, for example, Ccnd1 appear clearly in a subset of astrocytes (Fig.…”

NG2-Glia from Pallial Progenitors Produce the Largest Clonal Clusters of the Brain: Time Frame of Clonal Generation in Cortex and Olfactory Bulb

“…Still, a low number of clones are mainly restricted to corpus callosum, whose significance is unclear. It might be casuistic or be behind of particular characteristics of the callosal population, such as their electrophysiological profile (Chittajallu et al, 2004), their special potential as oligodendrocyte progenitors (Viganò et al, 2013), or a greater proliferative response to PDGF signaling (Hill et al, 2013).…”

“…Because NG2-glia death is uncommon in adult brain (Dawson et al, 2003), the fate of this proliferation is unclear. A significant oligodendrocyte generation in adult brain, throughout direct differentiation of NG2-glia (Zhu et al, 2011;Hughes et al, 2013), suggests this proliferation is a homeostatic response to replace these NG2 cells (Simon et al, 2011;Hughes et al, 2013). Furthermore, assuming a stable number between young and old animals, the outstanding cell increment in our NG2 clones should be concurrent with a size reduction of other nonlabeled NG2 clones.…”

“…In fact, polydendrocytes differ in the expression of molecular markers, such as glutamine synthetase (Karram et al, 2008) or myelin proteolipid protein (Mallon et al, 2002), as well as in their morphology or electrophysiological profile (Chittajallu et al, 2004;Káradó ttir et al, 2008;Ge et al, 2009). Similarly, NG2-glia also vary in their proliferative response to PDGF and potential as oligodendrocyte progenitors (Viganò et al, 2013) between gray and white matter (Hill et al, 2013).…”

Genetic Deletion ofCdc42Reveals a Crucial Role for Astrocyte Recruitment to the Injury SiteIn VitroandIn Vivo

“…A key aspect common to many injuries is the increase in astrocyte number at the injury site, which has been suggested to be a result of oriented migration and proliferation (Okada et al, 2006;Buffo et al, 2008;Simon et al, 2011). Given that the presence of astrocytes at the injury site is functionally important (Sofroniew, 2009), it is critical to understand the molecular machinery governing astrocyte polarity and recruitment to the injury site in vivo.…”