Altered ratios of alternatively spliced long and short γ2 subunit mRNAs of the γ-amino butyrate type A receptor in prefrontal cortex of schizophrenics
- 8 December 1998
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 95 (25), 15066-15071
- https://doi.org/10.1073/pnas.95.25.15066
Abstract
The relative abundance of alternatively spliced long (gamma2L) and short (gamma2S) mRNAs of the gamma2 subunit of the gamma-amino butyrate type A (GABAA) receptor was examined in dorsolateral prefrontal cortex of schizophrenics and matched controls by using in situ hybridization histochemistry and semiquantitative reverse transcription-PCR (RT-PCR) amplification. A cRNA probe identifying both mRNAs showed that the transcripts are normally expressed at moderately high levels in the prefrontal cortex. Consistent with previous studies, overall levels of gamma2 transcripts in prefrontal cortex of brains from schizophrenics were reduced by 28.0%, although this reduction did not reach statistical significance. RT-PCR, performed under nonsaturating conditions on total RNA from the same blocks of tissue used for in situ hybridization histochemistry, revealed a marked reduction in the relative proportion of gamma2S transcripts in schizophrenic brains compared with controls. In schizophrenics, gamma2S transcripts had fallen to 51.7% (+/-7.9% SE; P < 0.0001) relative to control levels. Levels of gamma2L transcripts showed only a small and nonsignificant reduction of 16. 9% (+/-12.0% SE, P > 0.05). These findings indicate differential transcriptional regulation of two functionally distinct isoforms of one of the major GABAA receptor subunits in the prefrontal cortex of schizophrenics. The specific reduction in relative abundance of gamma2S mRNAs and the associated relative increase in gamma2L mRNAs should result in functionally less active GABAA receptors and have severe consequences for cortical integrative function.Keywords
This publication has 57 references indexed in Scilit:
- Developmental expression of GABAA receptor subunit and GAD genes in mouse somatosensory barrel cortexJournal of Comparative Neurology, 1997
- An emerging pathophysiologyNature, 1997
- Schizophrenia research moves to the prefrontal cortexTrends in Neurosciences, 1994
- Short and Long Form γ2 Subunits of the GABAA/Benzodiazepine ReceptorsJournal of Neurochemistry, 1994
- Regulation of GABAA receptor function by protein kinase C phosphorylationNeuron, 1994
- Developmental and regional expression in the rat brain and functional properties of four NMDA receptorsNeuron, 1994
- GABAA receptor phosphorylation: multiple sites, actions and artifactsTrends in Pharmacological Sciences, 1991
- The γ3‐subunit of the GABAA‐receptor confers sensitivity to benzodiazepine receptor ligandsFEBS Letters, 1991
- Generation of Two Forms of the γ‐Aminobutyric AcidA Receptor γ‐2‐Subunit in Mice by Alternative SplicingJournal of Neurochemistry, 1991
- Importance of a novel GABAA receptor subunit for benzodiazepine pharmacologyNature, 1989