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Functional AMPA/kainate receptors in human embryonic and foetal central nervous system
M Bardoul1, C Levallois, N König
1INSERM U336 and EPHE Neurobiologie Cellulaire Quantitative, University of Montpellier II, France.
Insights
Functional AMPA/kainate receptors are present in the early human embryonic central nervous system. These receptors, identified in brainstem and spinal cord, are crucial for early brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Neuropharmacology
Background:
- AMPA/kainate receptors are critical ionotropic glutamate receptors involved in synaptic transmission.
- Understanding their role in early human development is essential for identifying potential developmental risks.
Purpose of the Study:
- To investigate the presence and function of AMPA/kainate receptors in the early human embryonic central nervous system.
- To characterize the distribution and properties of these receptors in developing brainstem and spinal cord.
Main Methods:
- Utilized the cobalt labeling method to detect functional AMPA/kainate receptors.
- Administered specific agonists (T-AMPA, kainate) and antagonists (KCl, NMDA) to assess receptor activity.
- Employed cyclothiazide to investigate receptor desensitization and regional differences.
Main Results:
- Demonstrated functional AMPA/kainate receptor expression in human embryonic and fetal brainstem and spinal cord tissue from 5.5 gestational weeks.
- Observed agonist-induced cobalt incorporation, particularly in motor regions.
- Found that cyclothiazide significantly enhanced staining in sensory regions, suggesting distinct receptor characteristics.
Conclusions:
- This study provides the first evidence of functional, divalent cation-permeable AMPA/kainate receptors in the early human CNS.
- Early embryonic exposure to substances affecting AMPA/kainate receptor activity may impact brain development due to calcium modulation.
Abstract:
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.