Subventricular Zone-Mediated Ependyma Repair in the Adult Mammalian Brain

Abstract

The subventricular zone (SVZ) of the adult mouse brain is a narrow stem cell niche that lies along the length of the lateral wall of the lateral ventricles. The SVZ supports neurogenesis throughout adulthood; however, with increasing age, the ventral SVZ deteriorates and only the dorsolateral SVZ remains neurogenic. Associated with the elderly dorsolateral SVZ, we reported previously an increased number of astrocytes interposed within the adjacent ependymal lining. Here, we show that astrocytes integrated within the ependyma are dividing, BrdU-labeled astrocytes that share cellular adherens with neighboring ependymal cells. By tracking BrdU-labeled astrocytes over time, we observed that, as they incorporated within the ependyma, they took on antigenic and morphologic characteristics of ependymal cells, suggesting a novel form of SVZ-supported "regenerative" repair in the aging brain. A similar form of SVZ-mediated ependyma repair was also observed in young mice after mild ependymal cell denudation with low dosages of neuraminidase. Together, this work identifies a novel non-neuronal mechanism of regenerative repair by the adult SVZ.

Ependymal cells along the lateral ventricle express functional P2X7 receptors

“…Recent evidence demonstrating regenerative repair in the ependymal layer from astrocytes [26] suggests that active signaling processes may be involved in maintaining a viable ependymal layer in health and during pathologic injury. Involvement of purinergic signaling and/or Ca 2+ -mediated second messenger pathways in initiating such repair is one intriguing possibility.…”

FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain

“…The emergence of these astrocytes between P19 and P21 is dependent on FoxJ1 expression as their density is severely depleted in the FoxJ1 -/-SVZ. Recent studies have described the expansion of a unique set of astrocytes in the aged ependymal layer (Luo et al, 2006), a phenomenon later shown to be involved in the repair of ependymal cells in elderly mice (Luo et al, 2008). It is possible that the small population of resident FoxJ1 + astrocytes might participate in the repair of the aged ependymal layer.…”

The Number of Stem Cells in the Subependymal Zone of the Adult Rodent Brain is Correlated with the Number of Ependymal Cells and Not with the Volume of the Niche

“…First, with reports documenting the importance of ependyma-derived factors such as regulators of bone morphogenetic proteins signaling, pigment epithelium-derived growth factor, and stromal cell-derived factor 1 in the control of NSC activity [23][24][25]. Second, with the evidence that adult NSCs can respond to ependymal cell loss by replacing the damaged cells [26]. They also corroborate observations in the early postnatal brain, when the maturation of adult NSCs follows the generation of ependymal cells [27], as well as in the ageing brain, where neurogenic activity is reduced in concert with the disappearance of ependymal cells [28].…”