Kalb R G, Lidow M S, Halsted M J, Hockfield S
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8502-6. doi: 10.1073/pnas.89.18.8502.
Quantitative receptor autoradiography was used to map the distribution of N-methyl-D-aspartate (NMDA) receptors in the developing rat spinal cord. Three different specific ligands, which label partially overlapping subpopulations of NMDA receptors, were used: an agonist (L-[3H]glutamate), a noncompetitive antagonist ([3H]MK-801), and a competitive antagonist ([3H]CGP-39653). In the adult, NMDA receptors labeled with all three ligands are restricted to the substantia gelatinosa in the spinal dorsal horn. In marked distinction, at postnatal day 7 NMDA receptors labeled with L-[3H]glutamate and [3H]MK-801 are present throughout the spinal gray matter. NMDA receptors in the neonatal spinal ventral horn have a higher affinity for L-[3H]glutamate than those in the adult substantia gelatinosa. Over the second and third postnatal weeks, NMDA receptors are lost from all areas of the spinal gray matter except for the substantia gelatinosa. Neonatal NMDA receptors identified with [3H]CGP-39653 are restricted to the substantia gelatinosa. These results show that the immature ventral horn contains a subpopulation of NMDA receptors and raise the possibility that motor neurons transiently express NMDA receptors in early postnatal life. Ventral horn NMDA receptors may be a component of the mechanisms by which the mature phenotype of motor neurons is acquired through activity-dependent processes. The loss of NMDA receptors over the course of development may play a role in limiting the period of motor neuron plasticity.
采用定量受体放射自显影术来绘制发育中大鼠脊髓中N-甲基-D-天冬氨酸(NMDA)受体的分布图。使用了三种不同的特异性配体,它们标记部分重叠的NMDA受体亚群:一种激动剂(L-[3H]谷氨酸)、一种非竞争性拮抗剂([3H]MK-801)和一种竞争性拮抗剂([3H]CGP-39653)。在成年大鼠中,用这三种配体标记的NMDA受体局限于脊髓背角的胶状质。与之形成显著差异的是,在出生后第7天,用L-[3H]谷氨酸和[3H]MK-801标记的NMDA受体遍布脊髓灰质。新生脊髓腹角中的NMDA受体对L-[3H]谷氨酸的亲和力高于成年胶状质中的NMDA受体。在出生后的第二和第三周,除胶状质外,脊髓灰质所有区域的NMDA受体均消失。用[3H]CGP-39653鉴定的新生NMDA受体局限于胶状质。这些结果表明,未成熟的腹角含有NMDA受体亚群,并增加了运动神经元在出生后早期短暂表达NMDA受体的可能性。腹角NMDA受体可能是运动神经元通过活动依赖过程获得成熟表型的机制的组成部分。发育过程中NMDA受体的丧失可能在限制运动神经元可塑性的时期中起作用。