Functional AMPA/kainate receptors in human embryonic and foetal central nervous system.
Here, functional AMPA/kainate receptors in human embryonic (5.5-7.5 gestational weeks) and foetal (8-10 gestational weeks) central nervous system tissue, shown by the cobalt labeling method, are reported. Specific agonist-induced cobalt incorporation was detected in brainstem and spinal cord cells, even in the youngest embryo studied. T-AMPA or kainate, but also vegetal toxins such as L-BOAA or acromelate, induced accumulation of cobalt. In contrast, no labeling was observed after exposure to KCl or NMDA. Cobalt labeled cells were particularly prominent in motor regions of brainstem and spinal cord. Co-application of the diuretic agent cyclothiazide, a desensitization blocker at AMPA receptors, dramatically increased the number of stained cells, which was particularly obvious in sensory regions, suggesting different receptor properties in motor versus sensory regions. This is the first study providing evidence for functional AMPA/kainate receptors, permeable to divalent 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 critical stages of embryogenesis to food or drug substances modifying the activity of AMPA/kainate receptors may alter brain development.
Bardoul
M
M
INSERM U336 and EPHE Neurobiologie Cellulaire Quantitative, University of Montpellier II, France.
Levallois
C
C
König
N
N
D000599:Amino Acids, Diamino / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D003035:Cobalt / Q000493:pharmacokinetics; D004622:Embryo, Mammalian; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D018091:Receptors, AMPA / Q000096:biosynthesis*; D018092:Kainic Acid Receptors / Q000096:biosynthesis*; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000599:Amino Acids, Diamino; D003035:Cobalt; D007608:Kainic Acid; D009498:Neurotoxins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C100126:oxalyldiaminopropionic acid; C051743:acromelic acid A