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Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
AMPA and metabotropic excitoxicity explain subplate neuron vulnerability
Vien Nguyen1, Patrick S McQuillen
1Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA.
Neurobiology of Disease
|October 14, 2009
Summary
Subplate neurons, crucial for brain development, are uniquely vulnerable to oxygen-glucose deprivation due to glutamate excitotoxicity. Novel mechanisms involving specific glutamate receptors contribute to this heightened sensitivity in developing brain cells.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Cerebral hypoxia-ischemia causes developmental brain injury via selective vulnerability of cell populations, notably subplate neurons.
- Glutamate excitotoxicity is a key mechanism implicated in this injury pattern.
Purpose of the Study:
- To investigate the role of glutamate excitotoxicity in the selective vulnerability of subplate neurons to hypoxia-ischemia.
- To compare the expression and function of glutamate receptors in subplate and cortical neurons.
Main Methods:
- Enriched cultures of subplate and cortical neurons were established.
- Glutamate receptor subunit expression profiles were determined using microarray and immunoblot.
- The excitotoxic effects of glutamate receptor agonists and antagonists were assessed.
Main Results:
- Subplate neurons exhibited greater sensitivity to oxygen-glucose deprivation than cortical neurons.
- Subplate neurons showed increased sensitivity to AMPA and reduced expression of the GluR2 subunit.
- Despite higher mGluR3 expression, group II mGluR agonists exacerbated, and antagonists reduced, subplate neuron death.
Conclusions:
- Selective vulnerability of subplate neurons to hypoxia-ischemia is partly mediated by glutamate excitotoxicity.
- Differential expression and function of glutamate receptors, particularly AMPA receptors and mGluR3, contribute to subplate neuron susceptibility.
- A novel mechanism involving group II metabotropic glutamate receptors may underlie subplate neuron vulnerability.
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