RNA editing (R/G site) and flip-flop splicing of the AMPA receptor subunit GluR2 in nervous tissue of epilepsy patients

Neurobiol Dis. 2004 Mar;15(2):371-9. doi: 10.1016/j.nbd.2003.11.006.

Abstract

Editing and alternative splicing of mRNA are posttranscriptional steps probably involved in pathophysiological aspects of epilepsy. The present study analyses the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit GluR2 with respect to the expression of (i) editing at the R/G site and (ii) flip-flop cassettes. Nervous tissue from patients with temporal lobe epilepsy was analysed by RT-PCR followed by restriction enzyme assays. Human autoptic tissue served as control. R/G editing status: the relative amount of edited RNA was significantly increased in the hippocampal tissue, whereas no changes were found in neocortical tissues. Flip-flop expression: no significant alterations were found in relative abundance of spliced variants containing the flip exon. The increased editing at the R/G site in the hippocampal tissue of epilepsy patients may enhance responses to glutamate, resulting in a synapse operating at an increased gain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alternative Splicing / genetics*
  • Child
  • Epilepsy, Temporal Lobe / genetics*
  • Epilepsy, Temporal Lobe / metabolism
  • Exons / genetics
  • Female
  • Hippocampus / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neocortex / metabolism*
  • RNA Editing / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, AMPA / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Temporal Lobe / metabolism

Substances

  • RNA, Messenger
  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 2