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Flip and flop splice variants of AMPA receptor subunits in the spinal cord of amyotrophic lateral sclerosis
Author(s) -
Tomiyama Masahiko,
RodríguezPuertas Rafael,
Cortés Roser,
Pazos Angel,
Palacios José M.,
Mengod Guadalupe
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10098
Subject(s) - ampa receptor , amyotrophic lateral sclerosis , spinal cord , motor neuron , neuroscience , biology , glutamate receptor , flip , receptor , medicine , genetics , disease , apoptosis
Excitotoxicity mediated by AMPA receptors has been suggested to be implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). To investigate the relevance of AMPA receptors to motor neuron degeneration in ALS, we evaluated the expression of mRNAs coding for flip and flop splice variants of AMPA receptor subunits (GluR‐A to GluR‐D) in the cervical segment of the spinal cord from control individuals and patients with ALS using in situ hybridization histochemistry. Transcript mRNAs coding for flop variants were significantly decreased in the ventral horn of the spinal cord from patients with ALS, whereas the mRNAs for flip variants were preserved. These findings suggest that the relative abundance of flip variants vs. flop variants is increased in spinal motor neurons of ALS patients when compared to that of control individuals. Flip variants promote assemblies of slowly desensitizing AMPA receptors. These results imply that spinal motor neurons of ALS patients possess more slowly desensitizing AMPA receptors than those of control individuals. This expression change of AMPA receptors in ALS may account for vulnerability of motor neurons in this disease. Synapse 45:245–249, 2002. © 2002 Wiley‐Liss, Inc.