Title

Age-Related Changes to the Subventricular Zone Stem Cell Niche

Date of Completion

January 2012

Keywords

Biology, Neurobiology|Biology, Physiology

Degree

Ph.D.

Abstract

Through adulthood the rodent subventricular zone (SVZ) stem cell niche generates new olfactory bulb interneurons. The SVZ stem cell niche is regulated by many components. In particular the ependymal monolayer that lines the ventricle surface is critical to maintain niche organization and function. The studies presented here examined changes to the ependymal monolayer and ventricle-contacting neural stem cells (NSCs) through aging. ^ While neurogenesis declines with age, specific changes to the NSC population have not been determined. Here, I conducted a spatio-temporal evaluation of adult SVZ NSCs, describing a decline in NSC numbers with age. Regional analysis along the lateral ventricle surface revealed that NSC loss is spatially uniform. Surprisingly, I found no significant change in the number of actively proliferating NSCs. Instead, my data reveal that although the total NSC number declines with age, the percentage of actively, mitotic NSCs increases, indicating that age-related declines in SVZ-mediated olfactory bulb neurogenesis occur downstream of NSC proliferation. ^ Following mild disruption of an intact ependyma in young adult mice, I have detected that proliferative cells from the SVZ generate new ependymal cells in an effort to maintain the integrity of the barrier. Additionally, extensive damage to the ependymal layer caused glial scarring at the ventricle surface and a subsequent deterioration of the underlying SVZ. ^ Comparative analysis of lateral ventricle volume and surface composition was performed using mouse and human tissue. I observed an intact, contiguous ependymal monolayer in mice throughout aging and mouse lateral ventricle size was maintained through aging. However, an age-related increase in human ventricle volume was observed. In addition, glial scarring at the ventricle surface was associated with the enlarged ventricles, indicating that humans typically do not maintain constant ventricle size or a contiguous ependymal barrier with age. Together this work contributes to our knowledge of age-related changes that occur at the ventricle surface in mice and humans and how these changes impact the underlying SVZ. ^