GluR2 glutamate receptor subunit flip and flop isoforms are decreased in the hippocampal formation in schizophrenia: a reverse transcriptase-polymerase chain reaction (RT-PCR) study.
Eastwood SL., Burnet PW., Harrison PJ.
GluR2 is the key subunit of heteromeric AMPA-preferring glutamate receptors. GluR2 mRNA has been shown by in situ hybridization histochemistry to be decreased in the hippocampal formation in schizophrenics. Here, a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method was used to investigate GluR2 expression further and to examine the relative abundance of its alternatively spliced mRNA isoforms ('flip' and 'flop') in 11 schizophrenics and 11 matched controls. Compared to the controls, schizophrenics showed reduced expression of both isoforms relative to cyclophilin mRNA, but a greater loss of the flop isoform led to a higher flip:flop ratio. These differences were observed having controlled for the confounding effects of brain pH and age upon the mRNAs. We also found that the abundance of GluR2 mRNA correlates with that of the encoded subunit. This study has confirmed that, in schizophrenia, hippocampal GluR2 mRNA is reduced, and indicates that GluR2 subunits are composed of a higher proportion of the flip variant. These data extend the evidence for glutamatergic dysfunction in the disease. They suggest that signal transduction through hippocampal AMPA receptors is impaired in schizophrenia both by an overall loss of GluR2 expression, and by the change in flip:flop ratio which is predicted to alter the desensitization kinetics of the remaining GluR2 subunits.