Deafferentation-induced increases in hippocampal insulin-like growth factor-1 messenger RNA expression are severely attenuated in middle aged and aged rats.

摘要

Deafferentation of the adult rat dentate gyrus induces reactive axonal growth by surviving afferent systems. In middle aged and aged rats, axonal sprouting is delayed and reduced relative to young adults. The cause for this age-related decline is not known, but it may reflect a decrement in trophic signals which initiate sprouting. Insulin-like growth factor-1 may play a role in sprouting because it (i) promotes axonal growth, (ii) is expressed at elevated levels by microglia just prior to sprouting onset, and (iii) is expressed with better spatiotemporal correspondence to hippocampal sprouting than other trophic factors examined. The present study used in situ hybridization to evaluate the influence of age on deafferentation-induced insulin-like growth factor-1 messenger RNA expression in the dentate gyrus. Messenger RNA levels were markedly elevated 4 days after an entorhinal cortex lesion at 3 months of age. Comparable lesions at 12 months did not significantly increase labeling whereas lesions at 18-26 months caused only a modest increase at 8 days postlesion. These data demonstrate that deafferentation induces more modest and delayed increases in insulin-like growth factor-1 expression in middle aged and aged rats than in young adults. The loss of reactive insulin-like growth factor-1 expression at ages exhibiting an attenuated sprouting response supports (i) an association between insulin-like growth factor-1 and sprouting and (ii) the possibility that impairments in the expression of this factor contributes to reduced axonal plasticity with age.