Differential effects of aging and insulin-like growth factor-1 on synapses in CA1 of rat hippocampus

Aging-related impairments of learning and memory can be ameliorated by 28 days of intracerebroventricular (icv) infusion of insulin-like growth factor-1 (IGF-1) in old rats. The present study investigated whether there is an aging-related synaptic decline in the stratum radiatum of hippocampal CA1 and whether IGF-1 can ameliorate that decline. Five young (4 months), five middle-aged (18 months) and five old (29 months) Fischer 344xBrown Norway rats received saline infusion; five old (29 months) rats received IGF-1 infusion for 28 days preceding sacrifice. Pyramidal neurons, total synaptic profiles as well as synaptic profiles in multiple spine bouton (MSB) complexes in CA1 were quantified stereologically with the physical disector technique and the postsynaptic density (PSD) length was determined as well. The results indicated a decrease of total synapses between middle and old age but a maintenance of PSD length and MSB synapses throughout life. IGF-1 infusion in old rats did not reverse the aging-related decline in total synapses but did increase PSD length and the number of MSB synapses. These changes in synaptic configurations are morphological correlates of enhanced synaptic efficacy. Thus, aging and IGF-1 affect different, but complementary, aspects of synapses in hippocampal CA1.