Studies on the effect of growth hormone on age-related changes in glutamatergic synaptic transmission in the hippocampus

Growth hormone (GH), a polypeptide hormone stored in and secreted by the pituitary, has been implicated in cognitive processing and maintenance of hippocampal function. Hippocampal function is mediated primarily by the AMPA and NMDA glutamatergic receptors, and these receptors are important for the basal synaptic transmission and long term potentiation (LTP) that underlie learning and memory processes. Cognitive function has been reported to decline with age, as reflected by a decline in performance on hippocampal-dependent tests of learning and memory. Parallel to this age-related cognitive decline is a reduction in the pulsatile release of GH. Chronic GH treatment has been observed to ameliorate the age-related cognitive decline. Furthermore, GH has been reported to enhance glutamatergic transmission in juvenile rats and to increase mRNA levels of subunits of the AMPA and NMDA types of glutamate receptors. The studies in this dissertation addressed whether deficits in glutamatergic synaptic transmission in old rats are mitigated by treatment with GH. Using an in vitro hippocampal slice model, direct application of GH acutely enhanced AMPA- and NMDA-dependent synaptic transmission in old as well as in young rats. Hippocampal slices from rats receiving 6 months of twice daily GH treatment also demonstrated increased AMPA- and NMDA-dependent synaptic transmission as well as enhanced LTP. These results demonstrate, for the first time, that GH can directly enhance glutamatergic transmission and synaptic plasticity in old rats when cognitive function demonstrates age-related decline.