The cause of the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) remains a mystery. One potential pathogenic mechanism is excitotoxicity due to disturbances of glutamatergic neurotransmission, particularly via AMPA-sensitive glutamate receptors. We report here that motor neurons from a familial ALS-linked superoxide dismutase (SOD1) mutant G93A mouse show an higher susceptibility to kainate-induced excitotoxicity. Moreover, they expressed GluR3 and GluR4 mRNA at detectable levels more frequently, with a modified electrophysiology when compared with control and wild-type SOD1 motor neurons. Thus, the SOD1 G93A mutation causes changes in the AMPA-receptor expression and function, as well as a susceptibility to kainate-mediated excitotoxicity, which may promote the motor neuron degeneration seen in ALS.
- Amyotrophic lateral sclerosis
- Glutamate receptors
- Motor neuron
- Mutated (Gly93→Ala) form of SOD1
- Selective vulnerability
- Superoxide dismutase-1
ASJC Scopus subject areas