1-甲基-4苯基吡啶離子引發神經毒性之研究

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. It is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. The intricate neurotoxic mechanisms underlying dopaminergic neurdegeneration still need to be elucidated. Nowadays, more and more emerging studies connect the pathogenic roles of glial cells in PD. Pro-inflammatory cytokines, such as interlukin (IL)-1β and tumor necrosis factor (TNF)-α were elevated in PD brains. In addition, the microglial activation is demonstrated to mediate the neurodegeneration process in PD. In this current experiment, we took the advantages of co-culture models of human neuroblastoma SH-SY5Y cell line and microglia–like THP-1 cell line; and studies the effect of MPP+ treatment on mono-cultured neurons and co-cultured neurons. In addition, we assessed the potential neuroprotection effects of antioxidants vitamin C and vitamin E on MPP+ and microglia-mediated neurotoxicity. Results from MTT assay showed that MPP+ treatment increased SH-SY5Y cell death in a dose-dependent manner. Differentiated SH-SY5Y cells are less sensitive to MPP+ treatment. Western blot analysis indicated that decreased phosphorylation of p38 is involved in both differentiation of SH-SY5Y and protected cells from MPP+ toxicity. Furthermore, neither vitamin C nor vitamin E effectively protects neurons from MPP+ insults. When compared with the mono-culture neurons, treatment of MPP+ significantly increased cell death in 24 hr in the co-culture group. However, there is no significant difference in cell viabilities between mono-culture and co-culture groups after 48 hr and 72 hr of MPP+ treatment. In addition, in co-culture system, vitamin C and vitamin E administration did not significantly protect neurons from MPP+ insult. Our results suggest that the microglia-neuron interaction might be a short term effect, and that oxidative stress may not be a primary cause of either MPP+-induced or microglia-mediated neurotoxicity in this event.