Martínez-Villayandre Beatriz, Paniagua Miguel Angel, Fernández-López Arsenio, Calvo Pedro
Dpto. Bioquímica y Biología Molecular; Facultad de Veterinaria, Universidad de León, 24007 León, Spain.
Brain Res. 2006 Oct 9;1114(1):19-23. doi: 10.1016/j.brainres.2006.07.002. Epub 2006 Sep 7.
We report the effects of the chronic treatments with the oxidant agent delta-aminolevulinic acid (ALA) and with the antioxidant vitamin E on the N-methyl-D-aspartate (NMDA) receptors in the striatum of 4-, 12- and 24-month-old male Wistar rats. ALA and vitamin E were administered daily for 15 days (40 mg/kg i.p. and 20 mg/kg i.p. respectively). NMDA receptors were labeled by membrane homogenate binding, using tritiated dizocilpine ([3H]MK-801). [3H]MK-801 binding in the striatum was significantly decreased at all ages in ALA-treated rats with respect to their controls, and in contrast, was significantly increased at all ages when rats received the treatment with vitamin E. Western blot assays were performed using antibodies against the NR2A subunit, a NMDA receptor subunit widely distributed in the brain. We did not find significant differences in the amounts of NR2A in rats treated with either ALA or vitamin E with respect to those rats not treated. We conclude that the NMDA receptor densities in the rat striatum are modified by the chronic treatment with oxidants and antioxidants in an age-independent way, at least until 24 months. Also, our results support the notion that NR2A is not involved in these modifications.
我们报告了用氧化剂δ-氨基乙酰丙酸（ALA）和抗氧化剂维生素E对4个月、12个月和24个月大的雄性Wistar大鼠纹状体中N-甲基-D-天冬氨酸（NMDA）受体进行长期治疗的效果。ALA和维生素E每天给药15天（分别为腹腔注射40mg/kg和20mg/kg）。使用氚标记的地佐环平（[3H]MK-801）通过膜匀浆结合对NMDA受体进行标记。与对照组相比，经ALA处理的大鼠在所有年龄段纹状体中的[3H]MK-801结合均显著降低，相反，当大鼠接受维生素E治疗时，在所有年龄段结合均显著增加。使用针对NR2A亚基（一种在脑中广泛分布的NMDA受体亚基）的抗体进行蛋白质免疫印迹分析。我们发现，与未治疗的大鼠相比，用ALA或维生素E治疗的大鼠中NR2A的含量没有显著差异。我们得出结论，至少在24个月之前，用氧化剂和抗氧化剂进行长期治疗以与年龄无关的方式改变了大鼠纹状体中NMDA受体的密度。此外，我们的结果支持NR2A不参与这些改变的观点。
