The First Hospital of Hebei Medical University, Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, China.
Brain Res. 2010 Jul 23;1345:213-20. doi: 10.1016/j.brainres.2010.05.043. Epub 2010 Jun 11.
Senescence-accelerated mouse prone 8 (SAMP8) has an early onset of senility and a shorter life span, providing with cognitive impairment. Contrasted with C57BL/6 mouse, which is most commonly used in the study of Parkinson's disease (PD), SAMP8 needs shorter period of breeding and might be good candidate for the investigation of cognitive impairment in PD. Studies had shown the increase of sensibility to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) with aging in C57BL/6 mouse. However, the sensitivity of MPTP neurotoxicity depends on the strains of animal and the exact mechanisms of the progression of PD promoted by aging is lack of consensus. Here, we showed after MPTP injection, the spontaneous activity of both young (3-month-old) and old (6-month-old) SAMP8 decreased dramatically, and the old mice required longer recovery time. Immunohistochemical and immunoblot analysis revealed that old mice displayed significant reductions in the dopaminergic neuron numbers and tyrosine hydroxylase (TH) protein. Microglia protein (CD11b) in the striatum of old mice increased more pronouncedly than that in the young mice from 24 h to 3 days. Inducible nitric oxide synthase (iNOS) in the striatum remarkably increased, however, no discernible difference between the two groups was found. These results suggested that the sensibility to MPTP increased with aging in SAMP8. A greater increase of microglial activation in old mice may be a possible mechanism to explain how advancing age predisposes the dopamine system to parkinsonism. The MPTP-SAMP8 model will start a new consideration for the study of PD.
衰老加速敏感 8 号小鼠（SAMP8）出现衰老提前和寿命缩短的现象，并伴有认知障碍。与最常用于帕金森病（PD）研究的 C57BL/6 小鼠相比，SAMP8 繁殖周期更短，可能是研究 PD 认知障碍的良好候选品。研究表明，C57BL/6 小鼠随着年龄的增长对 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的敏感性增加。然而，MPTP 神经毒性的敏感性取决于动物的品系，并且与衰老促进 PD 进展的确切机制仍缺乏共识。在这里，我们在 MPTP 注射后显示，年轻（3 个月大）和年老（6 个月大）SAMP8 的自发活动都显著下降，而年老小鼠需要更长的恢复时间。免疫组织化学和免疫印迹分析显示，年老小鼠的多巴胺能神经元数量和酪氨酸羟化酶（TH）蛋白明显减少。年老小鼠纹状体中的小胶质细胞蛋白（CD11b）从 24 小时到 3 天的增加比年轻小鼠更为明显。纹状体中的诱导型一氧化氮合酶（iNOS）明显增加，然而两组之间没有明显差异。这些结果表明 SAMP8 中 MPTP 的敏感性随年龄增长而增加。年老小鼠中小胶质细胞激活的增加可能是解释年龄增长如何使多巴胺系统易患帕金森病的一种可能机制。MPTP-SAMP8 模型将为 PD 的研究带来新的思考。
