Kalb R G, Fox A J
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J Comp Neurol. 1997 Jul 28;384(2):200-10. doi: 10.1002/(sici)1096-9861(19970728)384:2<200::aid-cne3>3.0.co;2-5.
Quantitative receptor autoradiography was used to map the distribution in the developing human spinal cord of the three types of ionotropic glutamate receptors. N-methyl-D-Aspartate (NMDA) receptors were labeled with [3H]glutamate, kainic acid (KA) receptors were labeled with [3H]KA, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA) receptors were labeled with [3H]AMPA. In the adult, labeling of all three receptor subtypes is largely restricted to the substantia gelatinosa (SG) in the dorsal horn, with very low level labeling elsewhere in the spinal gray matter. In marked distinction, in late fetal life, high level ligand binding is seen throughout the spinal gray matter. In early postnatal life, binding sites diminish in all regions, but least so in the SG, until the adult pattern emerges. Thus a coordinated transient high level of ionotropic glutamate receptor expression occurs within the developing spinal cord. Saturation analysis of ligand binding shows that the affinity of [3H]KA and [3H]AMPA binding is not developmentally regulated. In contrast, the affinity of [3H]glutamate binding to the NMDA receptor in the fetal ventral horn is three-fold greater than in the adult ventral horn. Thus, in addition to quantitative changes in glutamate receptor expression, qualitative changes occur in the expression of NMDA receptors during development. The distinct glutamate receptor phenotype of fetal and early postnatal spinal cord cells suggests that alterations in the excitable properties of these cells plays an important role in activity-dependent development and in susceptibility to excitotoxic injury.
采用定量受体放射自显影技术绘制了三种离子型谷氨酸受体在发育中的人类脊髓中的分布图谱。用[3H]谷氨酸标记N-甲基-D-天冬氨酸（NMDA）受体，用[3H] kainic酸（KA）标记海人藻酸（KA）受体，用[3H]α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）标记AMPA受体。在成年人中，所有三种受体亚型的标记主要局限于背角的胶状质（SG），脊髓灰质其他部位的标记水平非常低。与之形成显著区别的是，在胎儿后期，整个脊髓灰质中可见高水平的配体结合。在出生后早期，所有区域的结合位点都减少，但在SG中减少最少，直到出现成人模式。因此，在发育中的脊髓内会出现离子型谷氨酸受体表达的协调性短暂高水平。配体结合的饱和分析表明，[3H]KA和[3H]AMPA结合的亲和力不受发育调控。相比之下，胎儿腹角中[3H]谷氨酸与NMDA受体结合的亲和力比成人腹角大三倍。因此，除了谷氨酸受体表达的定量变化外，NMDA受体的表达在发育过程中还会发生定性变化。胎儿和出生后早期脊髓细胞独特的谷氨酸受体表型表明，这些细胞兴奋性特性的改变在活动依赖性发育和对兴奋性毒性损伤的易感性中起重要作用。
