RNA editing (Q/R site) and flop/flip splicing of AMPA receptor transcripts in young and old brains

Abstract

The effects of aging on the efficiency of RNA processing of AMPA glutamate receptor (GluR) subunits GluR1, GluR2, and GluR 3 was examined for RNA editing at the Q/R site of GluR2 and for alternative splicing of the flip or flop exons for GluR1–3. RNA isolated from six young (3 months old) and old (22–23 months old) animals was reverse-transcribed for PCR and restriction endonuclease analyses to distinguish between edited forms of GluR2 and flip/flop isoforms of GluR1–3. Unedited transcripts of GluR2 at the Q/R site (which controls calcium permeability) were not detected (at the limit of detection of ≥ 2.5%) from the corticies and hippocampi of young and old animals. Distribution of flop/flip isoforms in the cortex, hippocampus, hypothalamus, and striatum varied between GluR subunits and brain region, with GluR2 showing the greatest differences. However, no differences in alternative splicing of GluRs 1–3 were observed between young and old animals, suggesting that the fidelity of GluR transcript processing remains intact in the brains of aged animals.