Hashimoto Tomoyo, Nishi Katsunori, Nagasao Jun, Tsuji Sadatoshi, Oyanagi Kiyomitsu
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
Brain Res. 2008 Mar 4;1197:143-51. doi: 10.1016/j.brainres.2007.12.033.
A study was conducted to clarify the effects of magnesium (Mg) administration in a rat Parkinson disease (PD) model involving culture of ventral mesencephalic-striatal cells with 1-methyl-4-phenylpyridinium (MPP+), based on recent evidence for significant loss of dopaminergic neurons exclusively in the substantia nigra of 1-year-old rats after exposure to low Mg intake over generations [Oyanagi, K., Kawakami, E., Kikuchi-Horie, K., Ohara, K., Ogata, K., Takahama, S., Wada, M., Kihira, T., Yasui, M., 2006. Magnesium deficiency over generations in rats with special references to the pathogenesis of the parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Neuropathology 26, 115-128.]. The results indicated that Mg might protect dopaminergic neurons in the substantia nigra from degeneration. The concentration of Mg in the culture medium varied from 0.8 mM, corresponding to the control condition, to 4.0 mM. Effects were estimated by counting the number of surviving dopaminergic neurons immunopositive for tyrosine hydroxylase and measuring the length of dopaminergic neurites. An increase in the concentration of Mg to 1.2 mM significantly inhibited the toxicity of MPP+, and a concentration of 4.0 mM completely prevented any decrease in the number of dopaminergic neurons. The length of dopaminergic neurites was significantly preserved in the presence of Mg at 1.2 and 4.0 mM. An increase in the concentration of Mg to 1.2 and 4.0 mM led to a significant amelioration in the length of dopaminergic neurites after MPP+ toxicity. This is the first report to document a significant and striking effect of Mg for prevention of neurite and neuron pathology, and also amelioration of neurite pathology in a PD model.
基于近期证据表明，经过几代低镁摄入后，仅1岁大鼠黑质中的多巴胺能神经元会显著丧失[大柳圭、川上惠、菊池堀纪子、大原健、绪方健、高滨史、和田真人、木平知宏、安井正人，2006年。大鼠几代低镁摄入及其与关岛帕金森痴呆综合征和肌萎缩侧索硬化症发病机制的特别关联。神经病理学26卷，第115 - 128页。]，开展了一项研究以阐明镁（Mg）给药对大鼠帕金森病（PD）模型的影响，该模型涉及用1 - 甲基 - 4 - 苯基吡啶鎓（MPP +）培养腹侧中脑 - 纹状体细胞。结果表明，镁可能保护黑质中的多巴胺能神经元免于退化。培养基中镁的浓度从对应于对照条件的0.8 mM变化到4.0 mM。通过计数酪氨酸羟化酶免疫阳性的存活多巴胺能神经元数量以及测量多巴胺能神经突的长度来评估效果。将镁浓度增加到1.2 mM可显著抑制MPP +的毒性，而4.0 mM的浓度可完全防止多巴胺能神经元数量的任何减少。在镁浓度为1.2 mM和4.0 mM时，多巴胺能神经突的长度得到显著保留。将镁浓度增加到1.2 mM和4.0 mM可使MPP +毒性后多巴胺能神经突的长度得到显著改善。这是第一份记录镁对预防神经突和神经元病变以及改善PD模型中神经突病变具有显著且惊人效果的报告。
