Ionotropic glutamate receptor expression in human spinal cord during firsttrimester development

Quantitative receptor autoradiography and immunoblotting were used to study the expression and distribution of AMPA, kainate and NMDA receptors in fir st trimester human spinal cord obtained from elective abortions ranging fro m 4 to 11.5 weeks of gestational age. Spinal cord tissue sections were proc essed for receptor autoradiography with the ligands [H-3]AMPA, [H-3]kainate and [H-3]MK-801 and the optical density was measured separately in a dorsa l region (alar plate) and ventral region (basal plate) of the autoradiograp hs. Binding sites for all three ligands were demonstrated already at 4-5.5 weeks of gestation and increased continuously during the first trimester bo th in the dorsal and ventral regions. [H-3]AMPA binding to both high- and l ow-affinity sites increased from undetectable levels to about 35 and 400 fm ol/mg tissue, respectively, during this period. A temporal difference in th e distribution of [H-3]AMPA binding sites was observed. The early homogeneo us pattern of [H-3]AMPA binding in both alar and basal plates had changed t o a heterogeneous pattern at 11 weeks of gestation with the highest density of [H-3]AMPA binding sites in the superficial layers of the immature dorsa l horn. [H-3]kainate and [H-3]MK-801 binding sites were densely and homogen eously distributed already at 4 weeks, and steadily increased six-and two-f old, respectively, to about 100 fmol/mg tissue at 11.5 weeks of gestation. Immunoreactive bands corresponding to the NMDA receptor subunits NR1, NR2A, NR2B, NR2C and NR2D were demonstrated by immunoblotting at the earliest be tween 4.5 and 7 weeks and increasing concentrations were seen up to 11 week s of gestation. These results suggest that AMPA, kainate and NMDA receptors are expressed in the human spinal cord early in embryogenesis. (C) 2000 El sevier Science B.V. All rights reserved.