Alterations in insulin-like growth factor-1 gene and protein expression and type 1 insulin-like growth factor receptors in the brains of ageing rats
Section snippets
Animals
Young (three to four and 10–12 months), middle-aged (19–20 months), and old (29–32 months) male Fisher 344× Brown Norway rats (F1) were obtained from the National Institute of Ageing Colony at Harlan Industries (Indianapolis, IN) and housed in an specific pathogen-free facility on a 12:12 h light:dark cycle in a temperature-controlled room. Food (Prolab Rat/Mouse/Hamster 3000 Formula, PMI Feed, St Louis, MO) and water were available ad libitum. Animals were maintained in this facility for three
Insulin-like growth factor-1 gene expression in the meninges and cortical microvasculature
High levels of IGF-1 gene expression were observed in meninges across all age-groups. Although gene expression in this area was not specifically quantified, no differences were apparent between the three age-groups. Prominent IGF-1 gene expression was also observed in the arteries and arterioles of the somatosensory and frontal cortex, and expression was greater than that observed in cortical neurons. Fig. 1 and Fig. 2 show examples of localization of IGF-1 mRNA in cortical microvasculature by
Insulin-like growth factor-1, cerebrovasculature and brain ageing
Previous studies clearly demonstrate that IGF-1 has a trophic action on neurons. IGF-1 administration to cultured neurons has been shown to stimulate cell proliferation, survival, and neurite outgrowth52, 53, 68while, in vivo, IGF-1 has been reported to regulate synaptogenesis and myelin synthesis as well as neurotransmitter release.43, 44, 49, 58, 61, 70Although many of the actions of IGF-1 on neurons and glia are well-established, the source of IGF-1 that contributes to trophic support of
Conclusions
We have found that vascular endothelial cells within the CNS express IGF-1 mRNA and although expression is unchanged, the levels of IGF-1 protein decrease substantially with age. These changes occur concurrently with alterations in type 1 IGF receptor density providing strong evidence for withdrawal of IGF-1-related trophic support in the ageing brain. Since administration of IGF-1 has been shown to reverse several aspects of brain ageing, including cognitive deficits, we propose that
Acknowledgements
This research was supported by grant PO1 AG11370 from the National Institute on Ageing. Materials for the analysis of IGF-1 were the generous gift of the National Hormone and Pituitary Program and NIDDKD.
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