UC Berkeley

The generation of new neurons in the hippocampus in adult mammals, or adult hippocampal neurogenesis, is a potent source of plasticity in the brain. Adult neurogenesis is highly regulated by the organism’s environment, and stress is a powerful regulator of neurogenesis. Understanding the molecular basis of this stress-induced regulation helps us better appreciate the mechanisms and functional relevance of this fascinating process. Neurogenesis depends on the development of neural stem cells, which are tightly controlled by their surrounding cellular microenvironment, especially by a cell type of the brain that has shown to be highly important in regulating brain function, the astrocyte. The following studies describe how astrocyte-based signaling imparts key molecular regulatory mechanisms that are modulated by stress in the adult rat. Chapter 2 describes how an acute stressor enhances neural stem cell proliferation via astrocytic FGF2 signaling. Chapter 3 describes the suppression of stem cell proliferation by chronic stress via a late-onset astrocytic increase of BMP signaling. Taken together, these studies further advance our understanding of stress modulation of brain plasticity, and take into consideration an understudied cell type in stress biology, the astrocyte.