简介

Parkinson’s Disease (PD) is a neurodegenerative disease characterized by loss of the dopamine-containing neurons in the substantia nigra pars compacta (SNpc). Although the cause of neuronal death remains unclear, increasing evidence points to the role of chronic inflammatory processes. In order to explore the possibility that microglial activation causes dopaminergic cell death in the SNpc, lipopolysaccharide (LPS), a bacterial endotoxin that activate microglia, was into the substantia nigra (SN). The LPS injection not only caused the activation of microglia, but also resulted in a dose-dependent, selective loss of dopaminergic neurons by apoptosis in the SNpc. We therefore hypothesize that LPS activates microglia in the SN resulting in the release of cytotoxic agents. These agents, in turn, activate signal transduction pathways that cause neuronal degeneration of dopaminergic neurons in the SN. The long-term goal of this study is to validate LPS injection as a new animal model of PD that can be used to elucidate the etiology and molecular mechanisms underlying PD and to develop novel therapeutic treatments for this and other neurodegenerative diseases. Influence of Xenobiotic Metabolites on the Neuronal Cell Death Dr. Bing’s laboratory has recently found that a high level of microsomal epoxide hydrolase (mEH) expression in the brain of patients with Alzheimer’s disease as well as the rat brain following exposure to neurodegenerative agents such as kainic acid and trimethyl-tin. Relatively little is known about the expression and function of mEH in the CNS. However, the dual function of mEH in the activation as well as the inactivation of various reactive compounds from xenobiotic metabolites has important implications regarding its role in brain toxicity. The hypothesize is that mEH plays a crucial role in the biotransformation of endogenous xenobiotics and/or environmental chemicals into more toxic metabolites which may cause neuronal degeneration in specific neuronal populations. The identifying the exact role of mEH as well as the role of xenobiotic metabolites in the brain will be critical in understanding the neurodegeneration induced by exposure to toxic chemicals.