Stem cells reside in specialized niches that support their life-long self-renewal and differentiation. Adult neural stem cells continuously generate neurons in restricted parts of the brain that functionally integrate into neural circuits. These stm cells may represent an important source of endogenous cells that can be stimulated for brain repair. Defining the source and identity of signals from the niche that regulate adult neural stem cell behavior is essential to eventually harnessing these cells for brain repair, as well as understanding how changes in niche contribute to the decline in stem cell function that occurs with aging and disease. The subventricular zone (SVZ) is the largest germinal region in the adult brain and is located adjacent to the cerebrospinal fluid (CSF)-filled lateral ventricles. Although stem cells in this niche contact the CSF, the role of the CSF is largely unexplored. We propose here to: 1) determine the functional role of the CSF in the SVZ adult neural stem cell niche and how it is altered during aging, 2) define the role of candidate factors in the CSF compartment that change that mediate age-related changes in adult neural stem cell behavior and 3) perform comprehensive lipid profiling of young and aged mouse CSF.
This project will define the functional role of the cerebrospinal fluid in regulating adult neural stem cells, and how its effects change during aging. It will provie information about the microenvironment that supports the formation of new neurons in the adult mammalian brain and how neural stem cells are maintained throughout life. Understanding these cues will yield insight into the possibility of stimulating endogenous stem cells or activatig cells elsewhere in the brain for repair.
| Silva-Vargas, Violeta; Maldonado-Soto, Angel R; Mizrak, Dogukan et al. (2016) Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells. Cell Stem Cell 19:643-652 |
