| Summary: | 碩士 === 國立成功大學 === 行為醫學研究所 === 96 === We previously reported that lipopolysaccharide (LPS) treatment attenuated methamphetamine (MA)-induced nigrostriatal dopaminergic toxicity. This study was undertaken 1) to delineate the critical time window for the protective effects of LPS treatment against the MA-induced dopamine neurotoxicity and 2) to elucidate the underlying mechanism for such protective effects of LPS. We hereby reported that pretreatment with single LPS injection (1 mg/kg) one week before did not affect MA-induced nigrostriatal dopaminergic toxicity. An LPS injection (1 mg/kg) 72 hours before and 2 hours after the MA dosing protocol were effective to diminish the MA-induced nigrostriatal dopamine toxicity. Cytokine assay revealed that TNF-α, IL-1β, IL-6, IL-2, IL-5 and IFN-�� expressions were all elevated in striatal tissues following peripheral LPS treatment. We further demonstrated that nuclear NF�羠 activation in striatum was enhanced following single LPS injection. Finally, thalidomide, a TNF-α antagonist, pretreatment was found to abolish the LPS pretreatment-associated protective effects in this model. Taken together, these results suggest a critical time window for peripheral LPS treatment in exerting effective protection against MA-induced central dopamine toxicity. Moreover, such protective effects are mediated by enhanced TNF-α expression and/or NF�羠 activation in striatum. Such neuroprotective effects of LPS pretreatment was mitigated by anisomycin treatment, suggesting the roles of genetic expression and protein synthesis in mediating such neuroprotective effects.
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