Abstract
Stroke triggers neurogenesis in the striatum in mice, with new neurons deriving in part from the nearby subventricular zone and in part from parenchymal astrocytes. The initiation of neurogenesis by astrocytes within the striatum is triggered by reduced Notch-signaling, and blocking this signaling pathway by deletion of the gene encoding the obligate Notch coactivator Rbpj is sufficient to activate neurogenesis by striatal astrocytes in the absence of an injury. Here we report that blocking Notch-signaling in stroke increases the neurogenic response to stroke 3.5-fold in mice. Deletion of Rbpj results in the recruitment of a larger number of parenchymal astrocytes to neurogenesis and over larger areas of the striatum. These data suggest inhibition of Notch-signaling as a potential translational strategy to promote neuronal regeneration after stroke.
Highlights
Every year, 13.7 million people worldwide suffer a stroke, of whom 5.5 million die and as many suffer permanent loss of function with debilitating outcomes [1]
Neural stem cells differentiate into transit amplifying progenitor cells, which mature into neuroblasts, identified through the markers Doublecortin (Dcx) and Polysyalilated Neuronal Cell Adhesion Molecule (PSA-NCAM)
We report that deleting Rbpj in astrocytes results in an approximate doubling of the number of cells that enter the neurogenic program after a striatal stroke, with a concomitant increase in neuroblasts
Summary
13.7 million people worldwide suffer a stroke, of whom 5.5 million die and as many suffer permanent loss of function with debilitating outcomes [1]. In most parts of the brain, such as the cortex, there is no apparent neuronal replacement after stroke [2]. There is a regenerative response resulting in the replacement of a small proportion of the lost neurons [3,4]. Neurogenesis is abundant in the subventricular zone and in the dentate gyrus of the hippocampus in rodents and many other mammals. Neural stem cells differentiate into transit amplifying progenitor cells, which mature into neuroblasts, identified through the markers Doublecortin (Dcx) and Polysyalilated Neuronal Cell Adhesion Molecule (PSA-NCAM)
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