Synchronized overproduction of AMPA, kainate, and NMDA glutamate receptors during human spinal cord development

Abstract

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.

Altered Expression and Uptake Activity of Spinal Glutamate Transporters after Nerve Injury Contribute to the Pathogenesis of Neuropathic Pain in Rats

“…In contrast, the immunostaining pattern of GLT-1 was rather diffuse across the spinal dorsal horn. In general, the pattern of spinal GT distribution is in agreement with the role of GTs in regulating extracellular glutamate, because the highest density of glutamate receptors also is located primarily within the superficial spinal cord dorsal horn (Petralia et al, 1994a,b;Kus et al, 1995;Bonnot et al, 1996;Kalb and Fox, 1997).…”

Naltrexone-precipitated morphine withdrawal in infant rat is attenuated by acute administration of NOS inhibitors but not NMDA receptor antagonists

“…During development, NMDA receptors undergo qualitative and quantitative changes (Kalb et al 1992;Hori and Kanda 1994;Kalb and Fox 1997). These include alterations in density of the receptor (Morin et al 1989;Represa et al 1989;Tremblay et al 1988) and sensitivity to magnesium (Ben-Ari et al 1988;Bowe and Nadler 1990;Morrisett et al 1990) of NMDA receptors during the course of development.…”

“…The neonatal CNS is both structurally and functionally different from that of the adult, and significant changes in opioid actions occur both prenatally and postnatally (Barr 1992(Barr , 1993Fitzgerald 1995). At the same time, the NMDA receptor, which is believed to play an essential role in opiate dependence, undergoes qualitative and quantitative changes during development (Kalb et al 1992;Hori and Kanda 1994;Kalb and Fox 1997). There are significant developmental alterations both in the density of the receptor (Tremblay et al 1988;Morin et al 1989;Represa et al 1989) and in the sensitivity to magnesium (Ben-Ari et al 1988;Bowe and Nadler 1990;Morrisett et al 1990) of the NMDA receptor during the course of development.…”

Expression of the survival of motor neuron (SMN) gene in primary neurons and increase in SMN levels by activation of the N-methyl-D-aspartate glutamate receptor

“…These effects are produced through the activation of two general classes of glutamate receptors, the ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and the G-protein-coupled metabotropic receptors [23]. During the development of the spinal cord in both rodents and humans, the NMDA and non-NMDA receptor subtypes are expressed in a synchronized pattern and at high levels [24]. Moreover, during a circumscribed period in early post-natal life, motor neurons undergo activity dependent development that leads to the cell acquisition of mature molecular, physiological, and anatomical properties.…”