Reduced expression of insulin-like growth factor 1 messenger RNA in the hippocampus of aged rats.

Adult neurones remain dependent on neurotrophic factors such as insulin-like growth factor 1 (IGF-1) to sustain neuronal viability by maintaining cell phenotype, supporting synaptic plasticity and providing neuroprotective and neuroregenerative mechanisms. A decline in the cellular expression of neurotrophic factors has been speculated to contribute to the age-related changes that occur in the brain, where the hippocampus appears particularly susceptible. Using in situ hybridisation, we have made a detailed comparison of the expression of IGF-1 mRNA in the hippocampal formation between young (6 months) and aged (23 months) rats. IGF-1 mRNA expression was measured from cell populations containing only high density radioactive labelling (>20 grains/cell) to avoid ambiguity of signal. The amount of IGF-1 mRNA signal was significantly lower in cells of the alveus (P<0.05) and stratum lacunosum moleculare (P<0.01) of aged compared to young rats. These findings challenge reports that IGF-1 mRNA is unaltered in the ageing hippocampus and provide further evidence that changes in the IGF-1 system is a significant factor in the progressive age-related deterioration of normal neuronal function.