Schneider J S, Bradbury K A, Anada Yoshihiro, Inokuchi Jin-ichi, Anderson D W
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Brain Res. 2006 Jul 12;1099(1):199-205. doi: 10.1016/j.brainres.2006.04.114. Epub 2006 Jun 9.
A number of previous studies have demonstrated a positive effect of exogenously administered monosialoganglioside GM1 on striatal dopamine (DA) levels and DA neuron survival in animal models of parkinsonism. However, due to low bioavailability of peripherally administered GM1, the present study investigated the neuroprotective/neurorestorative potential of enhancing endogenous GM1 biosynthesis by administration of the synthetic ceramide analog L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (L-PDMP) in two mouse models of Parkinsonism produced by acute or subacute 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. L-PDMP treatment caused an increase in brain GM1 levels in both Parkinson models and resulted in a partial sparing of striatal DA levels in the subacute MPTP model but not in the acute MPTP model. L-PDMP treatment had no effect on DA neuron survival in either model. These data suggest that the administration of L-PDMP as a means to enhance endogenous brain GM1 levels may hold limited promise as a potential neuroprotective or neurorestorative therapeutic strategy for Parkinson's disease.
此前的多项研究已证明，在帕金森病动物模型中，外源性给予单唾液酸神经节苷脂GM1对纹状体多巴胺（DA）水平及DA神经元存活具有积极作用。然而，由于外周给予GM1的生物利用度较低，本研究在通过急性或亚急性给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）构建的两种帕金森病小鼠模型中，研究了通过给予合成神经酰胺类似物L-苏式-1-苯基-2-癸酰氨基-3-吗啉代-1-丙醇（L-PDMP）来增强内源性GM1生物合成的神经保护/神经修复潜力。L-PDMP治疗使两种帕金森病模型的脑GM1水平均升高，并使亚急性MPTP模型中的纹状体DA水平部分得以保留，但急性MPTP模型中未出现此现象。L-PDMP治疗对两种模型中的DA神经元存活均无影响。这些数据表明，作为提高脑内源性GM1水平的一种手段，给予L-PDMP作为帕金森病潜在的神经保护或神经修复治疗策略，其前景可能有限。
