GluR2 AMPA receptor subunit expression in motoneurons at low and high riskfor degeneration in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder that r esults in selective degeneration of most, but not all, groups of motoneuron s. The greater susceptibility of vulnerable motoneurons to glutamate excito toxicity and neurodegeneration has been hypothesized to result from their l ower expression of the GluR2 AMPA receptor subunit under control conditions , which renders these receptors permeable to calcium. To address the questi on of whether there is differential expression of the GluR2 subunit in moto neurons, we compared in normal adult rats expression of GluR2 mRNA and prot ein within two cranial motor nuclei that are either resistant (III; oculomo tor nucleus) or vulnerable (XII; hypoglossal nucleus) to degeneration in AL S. RT-PCR analysis of tissue punched from III and XII motor nuclei detected mRNA for all AMPA subunits (GluR1-R4). In situ hybridization demonstrated no significant difference in GluR2 mRNA expression between III and XII nucl ei, Immunohistochemical examination of GluR2 (and GluR4) protein levels dem onstrated a similar pattern of the subunit expression in both motor nuclei. This equivalent expression of GluR2 mRNA and protein in motoneurons that d iffer in their vulnerability to degeneration in ALS suggests that reduced e xpression of GluR2 is not a factor predisposing motoneurons to degeneration . (C) 2001 Academic Press.