Neurogenesis and the supply of new neurons to the olfactory bulb is the only currently acknowledged 'regenerative'feature of the adult brain subventricular zone (SVZ) stem cell niche in a non-injury situation. We propose a novel role for adult brain stem cells-- repair of the ependymal cell lining that overlies the SVZ. In preliminary work we found that with age the SVZ, the largest stem cell niche in the adult brain, shows signs of deterioration with a reduction in the production of new neurons. However, in what remains of the SVZ, we find regions of robust neurogenesis, even late in life. These neurogenic zones also show signs of active repair to the ependymal cell wall that overlies the SVZ and separates it from the brain's fluid-filled cavities, the ventricles. Ependymal cells provide a protective barrier and filtration system for the SVZ. In the elderly brain, we detect increased numbers of SVZ astrocytes interposed within the ependyma. These astrocytes develop adherens junctions with neighboring ependymal cells and display morphologic and antigenic characteristics of ependymal cells;they co-label with ependymal markers and possess multiple cilia, similar to ependymal cells. Interestingly, the stem cells of the SVZ were recently found to be a subpopulation of SVZ astrocytes. As a 5-year plan to examine stem cell-mediated repair in the aging brain, we will test the hypothesis that SVZ stem cells contribute to repair of the ependymal lining of the ventricle in elderly mice. We will also compare and contrast injury-induced repair in young adult mice to age-related repair in elderly mice. We propose that ependymal repair becomes necessary only late in life when gaps, left by dying ependymal cells or an expanding lateral ventricle, need to be filled. Support for this hypothesis would extend the regenerative functions of the SVZ to include ependymal repair--the first non-neuronal mechanism of regenerative repair identified for stem cells of the adult SVZ niche.
| Todd, Krysti L; Baker, Kasey L; Eastman, Matthew B et al. (2017) EphA4 Regulates Neuroblast and Astrocyte Organization in a Neurogenic Niche. J Neurosci 37:3331-3341 |
| Todd, Krysti L; Brighton, Tessa; Norton, Emily S et al. (2017) Ventricular and Periventricular Anomalies in the Aging and Cognitively Impaired Brain. Front Aging Neurosci 9:445 |
| Shook, Brett A; Lennington, Jessica B; Acabchuk, Rebecca L et al. (2014) Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain. Aging Cell 13:340-50 |
| Shook, Brett A; Manz, David H; Peters, John J et al. (2012) Spatiotemporal changes to the subventricular zone stem cell pool through aging. J Neurosci 32:6947-56 |
| Lennington, Jessica B; Pope, Sara; Goodheart, Anna E et al. (2011) Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone. J Neurosci 31:13078-87 |
| Conover, Joanne C; Shook, Brett A (2011) AGING OF THE SUBVENTRICULAR ZONE NEURAL STEM CELL NICHE. Aging Dis 2:149-163 |
| Villa, Max; Pope, Sara; Conover, Joanne et al. (2010) Growth of primary embryo cells in a microculture system. Biomed Microdevices 12:253-61 |
| Luo, Jie; Shook, Brett A; Daniels, Stephen B et al. (2008) Subventricular zone-mediated ependyma repair in the adult mammalian brain. J Neurosci 28:3804-13 |
