Evaluation of Early and Prolonged Effects of Acute Neurotoxicity and Neuroprotection Using Novel Functional Imaging Techniques

摘要

The wide use of herbicides and pesticides has increased the risk for environmental toxicity (Reiter et al 1998, Gorrell et al 1996). In addition, airborne environmental toxicity has continuously increased (Zayed et al 1996). In addition, recent findings suggest that environmental proteasome inhibitors, like naturally occurring epoximicin, are candidates for Parkinson's disease causing toxins (McNaught, 2004). Exogenous and endogenous neurotoxicity present a major challenge in developing specific and sensitive in vivo methods to determine pathophysiological mechanisms of toxins. This information is essential in order to design new methods for neuroprotection and therapy. Our overall research goal proposed to develop and improve in vivo imaging techniques to examine neurofunction of dopaminergic and glutamatergic receptors as well as oxidative glucose metabolism and neurochemicals. High resolution imaging techniques were developed and used to explore the excitotoxicity induced regional neuronal dysfunction in functional and metabolic pathway. The neuronal toxicity models included two animal models: rats with 3-nitropropionic acid induced striatal lesions and transgenic mice with gene expression of human Huntington's disease (HD). In the final phase of this project we tested neuroprotection with novel newly developed ligands effecting on metabotropic glutamate receptor function as well as a ligand, which is a transglutaminase inhibitor.