Age-related effects of IGF-1 on the NMDA-, GH- and IGF-1-receptor mRNA transcripts in the rat hippocampus.

Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) have been suggested to promote memory and cognitive capabilities. In a recent publication we observed that GH increase the proportion of the NR2B subunit mRNA transcript of the NMDA receptor in rat hippocampus. NR2B has been suggested to be essential for spatial learning and long-term potentiation (LTP). This effect of GH might be IGF-1-mediated or a result of a co-ordination with IGF-1. To test this hypothesis further, we examined the effects of 10 daily s.c. injections of IGF-1 on NMDA receptor subunits (NR1, NR2A, and NR2B), GH receptor (GHR), GH binding protein (GHBP) and type 1 IGF receptor (IGF-1R) gene transcripts in the hippocampus. The NR2B subunit mRNA increased in young (11 weeks) but not in older (14-16 months) rats and the expression of the NR2A mRNA was decreased in both groups. The ratio of NR2B to NR2A is suggested to mirror the potential for synaptic plasticity. In both age groups, IGF-1 treatment resulted in a significant increase of this ratio at transcription level. The GHR mRNA increased in young rats, mimicking the effect of GH, while the IGF-1R mRNA was decreased in the older group of rats after IGF-1 treatment. These results suggest that IGF-1 in many aspects may mediate the actions earlier shown for GH.