The objective of this research is to understand the role of adrenal steroids in mediating normal cerebellar development and to establish the mechanisms by which developmental events are perturbed in response to high concentrations of glucocorticoids. Postnatal administration of glucocorticoids disrupts cerebellar development and causes functional deficits involving locomotor activity in motor coordination. Granule neuron progenitors are potential targets for glucocorticoids since they are responsible for defining a critical period of postnatal development in the cerebellum. However, it is unclear whether glucocorticoids intrinsically effect cerebellar development. Furthermore, the direct effects or precise mechanisms of action on granule neuroblast cell division or cell survival have not been systematically explored.
The specific aims of this proposal are 1) test the hypothesis that glucocorticoids attenuate granule neuroblast proliferation and 2) characterize the influence of glucocorticoids on EGL cell turnover by simultaneously evaluating both cell proliferation and survival. These studies will be performed in a noel EGL murine cell culture using biochemical, morphometric and flow cytometric techniques. Results from these experiments should provide clinically relevant insight regarding the neurodevelopmental consequences attributable to postnatal stress or administration of glucocorticoids in the neonate.
