Abstract
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 GluR(3) and GluR(4) 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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Alanine / genetics
-
Alanine / metabolism
-
Amyotrophic Lateral Sclerosis / enzymology*
-
Amyotrophic Lateral Sclerosis / genetics*
-
Animals
-
Cells, Cultured
-
Drug Resistance / genetics
-
Fetus
-
Genetic Predisposition to Disease / genetics
-
Glycine / genetics
-
Glycine / metabolism
-
Kainic Acid / pharmacology
-
Membrane Potentials / drug effects
-
Membrane Potentials / genetics
-
Mice
-
Mice, Transgenic
-
Motor Neurons / drug effects
-
Motor Neurons / enzymology*
-
Motor Neurons / pathology
-
Mutation / genetics*
-
Neurotoxins / pharmacology
-
Protein Subunits / drug effects
-
Protein Subunits / genetics
-
Protein Subunits / metabolism
-
RNA, Messenger / metabolism
-
Receptors, AMPA / drug effects
-
Receptors, AMPA / genetics
-
Receptors, AMPA / metabolism*
-
Superoxide Dismutase / genetics*
-
Synaptic Transmission / drug effects
-
Synaptic Transmission / genetics
Substances
-
Neurotoxins
-
Protein Subunits
-
RNA, Messenger
-
Receptors, AMPA
-
glutamate receptor ionotropic, AMPA 3
-
glutamate receptor ionotropic, AMPA 4
-
Superoxide Dismutase
-
Alanine
-
Kainic Acid
-
Glycine