Villayandre Beatriz Martínez, Paniagua Miguel Angel, Fernández-López Arsenio, Calvo Pedro
Departamento Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad de León, 24007 León, Spain.
Brain Res. 2005 Nov 9;1061(2):80-7. doi: 10.1016/j.brainres.2005.08.001. Epub 2005 Oct 17.
We report here the effects of the chronic treatment with the oxidant agent delta-aminolevulinic acid (ALA) on the N-methyl-D-aspartate (NMDA) receptors in 4-, 12- and 24-month-old male Wistar rats. ALA was administered daily for 15 days (40 mg/kg i.p). The study was performed by membrane homogenate binding and autoradiography, using tritiated 5-methyl-10, 11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate ([3H]MK-801). [3H]MK-801 binding was significantly decreased in most areas studied (cortex and hippocampus) at all ages in treated rats with respect to their controls. Furthermore, Western blot assays were performed using antibodies against the NMDA receptor NR2A subunit, which is widely distributed in the brain, mainly in cortex and hippocampus. In cortex but not in hippocampus, the ALA treatment induced significant decreases in the amounts of NR2A subunit in 12- and 24-month-old animals. We conclude that chronic treatment with ALA is able to induce NMDA receptor decreases in an age-independent way and that NR2A subunit seems to be involved in these decreases in cerebral cortex, but not in the other structures studied.
我们在此报告，用氧化剂δ-氨基乙酰丙酸（ALA）对4个月、12个月和24个月大的雄性Wistar大鼠进行长期治疗，对其N-甲基-D-天冬氨酸（NMDA）受体的影响。每天腹腔注射ALA 40mg/kg，持续15天。该研究采用膜匀浆结合法和放射自显影法，使用氚标记的马来酸5-甲基-10,11-二氢-5H-二苯并[a,d]环庚烯-5,10-亚胺（[³H]MK-801）。与对照组相比，在所有年龄段的受试大鼠中，大多数研究区域（皮层和海马体）的[³H]MK-801结合均显著降低。此外，使用针对NMDA受体NR2A亚基的抗体进行蛋白质免疫印迹分析，该亚基广泛分布于大脑中，主要在皮层和海马体中。在皮层而非海马体中，ALA处理导致12个月和24个月大动物的NR2A亚基含量显著降低。我们得出结论，ALA长期治疗能够以与年龄无关的方式诱导NMDA受体减少，并且NR2A亚基似乎参与了大脑皮层中这些受体的减少，但在其他研究结构中并非如此。
