FUNCTIONAL AMPA KAINATE RECEPTORS IN HUMAN EMBRYONIC AND FETAL CENTRAL-NERVOUS-SYSTEM/

Here, functional AMPA/kainate receptors in human embryonic (5.5-7.5 ge stational weeks) and foetal (8-10 gestational weeks) central nervous s ystem tissue, shown by the cobalt labeling method, are reported. Speci fic agonist-induced cobalt incorporation was detected in brainstem and spinal cord cells, even in the youngest embryo studied. T-AMPA or kai nate, but also vegetal toxins such as L-BOAA or acromelate, induced ac cumulation of cobalt. In contrast, no labeling was observed after expo sure to KCl or NMDA. Cobalt labeled cells were particularly prominent in motor regions of brainstem and spinal cord. Go-application of the d iuretic agent cyclothiazide, a desensitization blocker at AMPA recepto rs, dramatically increased the number of stained cells, which was part icularly obvious in sensory regions, suggesting different receptor pro perties in motor versus sensory regions. This is the first study provi ding evidence for functional AMPA/kainate receptors, permeable to diva lent cations, in brainstem and spinal cord at an early stage of human central nervous system development. Since many developmental processes are influenced by the modulation of cytosolic calcium, exposure at cr itical stages of embryogenesis to food or drug substances modifying th e activity of AMPA/kainate receptors may alter brain development. (C) 1998 Elsevier Science B.V. All rights reserved.