Journal
NEUROSCIENCE
Volume 99, Issue 2, Pages 305-316Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0306-4522(00)00200-1
Keywords
IGF-1; tau; phosphorylation; primary cortical neuron; lithium; glycogen synthase kinase-3 beta
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Funding
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS035060] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P01AG006569] Funding Source: NIH RePORTER
- NIA NIH HHS [AG06569] Funding Source: Medline
- NINDS NIH HHS [NS35060] Funding Source: Medline
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The modulation of tau phosphorylation and localization in response to insulin-like growth factor-1 or insulin was examined in primary cultures of rat cortical neurons. Insulin and insulin-like growth factor-1 treatment resulted in a rapid and transient increase in tau phosphorylation at specific epitopes. These effects were completely inhibited by lithium, revealing that the insulin and insulin-like growth factor-1 induced changes in tau phosphorylation were mediated by glycogen synthase kinase-3 beta. In addition, the increase in tau phosphorylation directly correlated with a transient dissociation of tau from the cytoskeleton, indicating that insulin and insulin-like growth factor-1 treatment resulted in a change in tau localization. Using immunocytochemistry, it was also demonstrated that treatment of neurons with insulin-like growth factor-1 for 3 min resulted in a redistribution of tau to the growth cone and the distal segment of the axons. Further, insulin-like growth factor-1 treatment resulted in an increased immunoreactivity with the phospho-dependent antibody AT8 in the same areas of the axons. Thus, the phosphorylation state and distribution of tau can be modulated by insulin and insulin-like growth factor-1 signaling pathways involving glycogen synthase kinase-3 beta. We propose that by transiently increasing tau phosphorylation, insulin and insulin-like growth factor-1 may contribute to the reorganization of the cytoskeleton necessary for the development and growth of the neurites. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.
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