Evaluation of Neurogenesis and Synaptic Plasticity in the YAC128 Transgenic Mouse Model of Huntington's Disease

Currently, there are no therapeutic options available to help regenerate lost brain tissue in patients with Huntington’s disease (HD). However, a large body of evidence suggests that the adult brain retains a limited ability to generate new neurons (a process called neurogenesis), and that adult neuronal stem cells that underlie this process may be a possible endogenous source of healthy neurons for the treatment of certain neurodegenerative diseases including HD. Significant strides are being made in understanding how neural stem cells could be used in regenerative transplant therapies in a number of pathologies. However, whether a ""diseased"" brain has the capacity to sustain regenerative therapy remains unclear. Jessica Simpson is studying how HD affects two populations of endogenously active neuronal stem cells. These stem cells normally give rise to new neurons through out life, so they offer an endogenous indicator of how HD is affecting the brains capacity to regenerate. In addition, she will be testing whether non-invasive therapies aimed at restoring adult neurogenesis and synaptic plasticity (i.e. voluntary physical exercise), might be beneficial in reversing some of the cognitive as well as neuropathological and motor deficits seen in HD mouse models. Adult neurogenesis and synaptic plasticity are thought to be involved in cognitive function, namely learning and memory, in the normal adult brain. Her studies will improve our existing knowledge of how adult neurogenesis and synaptic plasticity are affected in the HD brain and thereby improve our knowledge of the pathogenic mechanisms triggered by HD at the neuronal level. Ms. Simpson's research may lead to the development of restorative therapeutic strategies that recruit endogenous stem cells into degenerated areas of the brain. Such strategies might also be useful for the treatment of other neurodegenerative diseases characterized by the loss of specific neuronal populations such as Parkinson's disease. Moreover, the results from this study could potentially contribute to the growing body of evidence suggesting that the use of non-invasive therapeutic strategies, such as voluntary physical exercise and environmental enrichment, provide benefit in the treatment of neurodegenerative conditions such as Alzheimer's disease.