Altered ratios of alternatively spliced long and short gamma 2 subunit mRNAs of the gamma-amino butyrate type A receptor in prefrontal cortex of schizophrenics

作者：Huntsman MM; Tran BV; Potkin SG; Bunney WE; Jones EG^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 1998, 95(25): 15066-15071.

DOI：10.1073/pnas.95.25.15066

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 (GABA(A)) 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 precious 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 sial 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 GABA(A) 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 GABA(A) receptors and have severe consequences for cortical integrative function.

• 出版日期1998-12-8