Abstract
Stem cell – based therapies for central nervous system disorders are intensely pursued. Such approaches can be divided into two categories: Transplantation-based, and those that aim to pharmacologically target the endogenous stem cell population in the tissue. Endogenous stem cell – based strategies avoid the problem of immune incompatibility between the host and the grafted cells. They also avoid the placement of a large amount of cells in confined areas, a manipulation which alters the characteristics of the neurovascular microenvironment. We show here that massive pharmacological activation (increase in cell numbers) of the endogenous neural stem cell population in the adult rodent brain maintains the cytoarchitecture of the neurovascular niche. Distances between adjacent stem cells (identified by expression of Hes3) are maintained above a minimum. Hes3+ cells maintain their physical association with blood vessels. These results also suggest a mechanism by which the activation signal from the lateral ventricle can be propagated to areas a long distance away from the lateral ventricles, through autocrine/paracrine actions between adjacent Hes3+ cells, along blood vessels. Finally, powerful effects of angiopoietin 2 on Hes3+ cells help explain the prevalence of proliferating endogenous neural stem cells close to the subventricular zone (an area of high angiopoietin 2 concentration) and the quiescent state of stem cells away from the ventricles and their tight physical association with blood vessels (which express high levels of angiopoietin 1, a cytokine that opposes angiopoietin 2 functions).
Highlights
The adult mammalian central nervous system retains a population of immature cells
It is commonly agreed that in the adult mammalian brain, the subventricular zone is home for multipotent neural stem cells; stem cells or progenitor cells are found in the dentate gyrus of the adult hippocampus [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42]
In this paper we address a specific feature of the neurovascular niche: Why the majority of endogenous neural stem cells are located in the subventricular zone lining the lateral ventricles of the adult brain
Summary
The adult mammalian central nervous system retains a population of immature cells (multipotent stem cells and more restricted neural progenitor cells). It is commonly agreed that in the adult mammalian brain, the subventricular zone (the area lining the lateral ventricles of the brain) is home for multipotent neural stem cells; stem cells or progenitor cells are found in the dentate gyrus of the adult hippocampus [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42] Both these areas are neurogenic and provide new neurons involved in olfaction
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