The recent discovery of stem cells in the adult human brain that are capable of proliferating and becoming new neurons is a promising new development for the treatment of neurodegenerative diseases and other conditions, such as traumatic brain injury, where neurons are lost and neurogenesis is needed. While we know that these stem cells are regulated by factors such as diet, exercise, antidepressant drugs, and stress, the mechanisms that govern these cells and their role in adult neurogenesis are not well understood. The Levenson lab uses rodent models as well as cultured human neuronal precursor cells to understand the cellular and molecular mechanisms that are responsible for proliferation, survival, and differentiation of adult stem cells in the brain.

Our lab has shown that the trace element zinc regulates adult stem cells in the subgranular zone of the adult dentate gyrus. Thus, we are working to identify and study the cellular and molecular mechanisms that govern the role of zinc in adult stem cell survival, neuronal precursor proliferation, and neuronal differentiation. The importance of these cells in the hippocampus is illustrated by recent observations that antidepressant drugs enhance the survival of adult stem cells in this region of the brain. This information, coupled with our recent findings that zinc deficiency induces depression-like and anxiety-like behaviors and impairs the efficacy of the commonly prescribed antidepressant drug, fluoxetine, suggests an important role for zinc not only in adult neurogenesis, but also in the behaviors that it controls. Thus, our current work is designed to examine the zinc-regulated nuclear and mitochondrial factors, such as the tumor suppressor protein p53, that are responsible for the regulation of adult stem cells and neurogenesis.

Neuronal injury and death appears to be a trigger for stem cell proliferation and adult neurogenesis. Every year 1.5 million Americans sustain a traumatic brain injury (TBI). Among the long list of impairments that can result from TBI, including loss of both fine and gross motor skills as well as speech and language abilities, many patients also experience life-long impairment of learning, memory and cognitive function. The Levenson lab is exploring ways to promote neuronal survival after traumatic brain injury, induce neurogenesis, and improve behavioral outcomes. In collaboration with Dr. Jacob VanLandingham, of the College of Medicine, and Dr. Victor Schepkin at the National High Magnetic Field Laboratory we have been using a variety of hormonal and dietary approaches to treat traumatic brain injury including caloric restriction, vitamin D, and progesterone. Not only have we shown significant improvements in learning and memory after brain injury, we are able to track changes in cytotoxic and vasogenic edema using novel diffusion-weighted magnetic resonance imaging at 21 Tesla.