标题：Altered ratios of alternatively spliced long and short γ2 subunit mRNAs of the γ-amino butyrate type A receptor in prefrontal cortex of schizophrenics
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：25
页码：15066-15071
DOI：10.1073/pnas.95.25.15066
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The relative abundance of alternatively spliced long ({gamma}2L) and short ({gamma}2S) mRNAs of the {gamma}2 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 {gamma}2 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 {gamma}2S transcripts in schizophrenic brains compared with controls. In schizophrenics, {gamma}2S transcripts had fallen to 51.7% ({+/-}7.9% SE; P < 0.0001) relative to control levels. Levels of {gamma}2L 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 {gamma}2S mRNAs and the associated relative increase in {gamma}2L mRNAs should result in functionally less active GABAA receptors and have severe consequences for cortical integrative function.
