Tamaru M, Yoneda Y, Ogita K, Shimizu J, Nagata Y
Department of Physiology, Fujita Health University School of Medicine, Aichi, Japan.
Brain Res. 1991 Feb 22;542(1):83-90. doi: 10.1016/0006-8993(91)91001-h.
Binding activities of central excitatory amino acid receptors were examined in Triton-treated membrane preparations of the cerebral cortex and hippocampus from brains of rats at 2, 7 and 29 months after birth. Aged rats exhibited a significant reduction of [3H]glutamate (Glu) binding displaceable by N-methyl-D-aspartate (NMDA), as well as strychnine-insensitive [3H]glycine binding in both central structures, as compared with those in young rats. Binding of 3H-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate (MK-801), a non-competitive NMDA antagonist used to label the activated state of ion channels linked to NMDA-sensitive receptors, also decreased with aging irrespective of the experimental conditions employed. Scatchard analysis revealed that reduction of both [3H]Glu binding and [3H]MK-801 binding were due to a significant decrease in the densities of binding sites with aging, with their affinities being unaltered. Binding of [3H]D,L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), which is a specific agonist for quisqualate-sensitive receptors, was unchanged with aging when determined in the absence of 100 mM potassium thiocyanate (KSCN). However, AMPA binding determined in the presence of added KSCN was about 25% reduced in both brain regions of aged rats. Binding of [3H]kainate to kainate-sensitive receptors was unchanged with aging. These results suggest that glutaminergic neurotransmission mediated by NMDA-sensitive receptors may be selectively impaired with aging in the hippocampus and cerebral cortex among 3 different subclasses of excitatory amino acid receptors in the brain.
在出生后2个月、7个月和29个月大鼠的大脑中，检测了大脑皮层和海马经 Triton 处理的膜制剂中中枢兴奋性氨基酸受体的结合活性。与年轻大鼠相比，老年大鼠在这两个中枢结构中，N - 甲基 - D - 天冬氨酸（NMDA）可置换的[3H]谷氨酸（Glu）结合以及士的宁不敏感的[3H]甘氨酸结合均显著降低。3H-5 - 甲基 - 10,11 - 二氢 - 5H - 二苯并[a,d]环庚烯 - 5,10 - 亚胺马来酸盐（MK - 801）是一种用于标记与NMDA敏感受体相连的离子通道激活状态的非竞争性NMDA拮抗剂，其结合也随衰老而降低，与所采用的实验条件无关。Scatchard分析表明，[3H]Glu结合和[3H]MK - 801结合的减少是由于结合位点密度随衰老显著降低，而其亲和力未改变。在不存在100 mM硫氰酸钾（KSCN）的情况下测定时，作为quisqualate敏感受体特异性激动剂的[3H]D，L-α-氨基-3 - 羟基-5 - 甲基异恶唑-4 - 丙酸（AMPA）结合随衰老未发生变化。然而，在添加KSCN的情况下测定时，老年大鼠两个脑区的AMPA结合均降低约25%。[3H]海人藻酸与海人藻酸敏感受体的结合随衰老未发生变化。这些结果表明，在大脑兴奋性氨基酸受体的3种不同亚类中，由NMDA敏感受体介导的谷氨酰胺能神经传递可能在衰老过程中在海马和大脑皮层中受到选择性损害。
