The Effect of Growth Hormone on mRNA Expression of the GABA_B1Receptor Subunit and GH/IGF Axis Genes in a Mouse Model of Prader-Willi Syndrome

Abstract

Purpose: Growth hormone (GH) therapy substantially improves several cognitive functions in PWS. However, the molecular mechanisms underlying the beneficial effects of GH on cognition remain unclear in PWS. In this study, we investigated the effects of recombinant human GH on the gene expression of GABAB receptor subunits and GH/insulin-like growth factor (IGF) axis genes in the brain regions of PWS-mimicking mice (Snord116del). Methods: Snord116del mice were injected subcutaneously with 1.0 mg/kg GH or saline, once daily for 7 days. The collected brain tissues were analyzed for mRNA content using quantitative PCR (qPCR) in the cerebellum, hippocampus, and cerebral cortex. Results: GH increased the mRNA expression level of the GABA B1 receptor subunit (GABA BR1 ) and IGF-1R in the cerebellum. Furthermore, a significant positive correlation was found between the level of GABA BR1 mRNA and the expression of the IGF-1R transcript. GH also induced an increase in the mRNA expression of IGF-2 and IGF-2R in the cerebellum. Conclusion: These data indicate that GH may provide beneficial effects on cognitive function through its influences on the expression of GABA BR1 and GH/IGF-1 axis genes in PWS patients.