A critical role for IGF-II in memory consolidation and enhancement – Nature.com

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Nature volume 469, pages 491–497 (2011)Cite this article
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We report that, in the rat, administering insulin-like growth factor II (IGF-II, also known as IGF2) significantly enhances memory retention and prevents forgetting. Inhibitory avoidance learning leads to an increase in hippocampal expression of IGF-II, which requires the transcription factor CCAAT enhancer binding protein β and is essential for memory consolidation. Furthermore, injections of recombinant IGF-II into the hippocampus after either training or memory retrieval significantly enhance memory retention and prevent forgetting. To be effective, IGF-II needs to be administered within a sensitive period of memory consolidation. IGF-II-dependent memory enhancement requires IGF-II receptors, new protein synthesis, the function of activity-regulated cytoskeletal-associated protein and glycogen-synthase kinase 3 (GSK3). Moreover, it correlates with a significant activation of synaptic GSK3β and increased expression of GluR1 (also known as GRIA1) α-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid receptor subunits. In hippocampal slices, IGF-II promotes IGF-II receptor-dependent, persistent long-term potentiation after weak synaptic stimulation. Thus, IGF-II may represent a novel target for cognitive enhancement therapies.
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In Supplementary Fig. 2 of this Article, the same western blot representative was inadvertently used for rows 1 and 3 of the left panel.
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Acknowledgments This work was supported by grants R01-MH065635, R01-MH074736, NARSAD, the Hirschl Foundation and Philoctetes Foundation awarded to C.M.A., F31-MH816213 to D.Y.C., and T32-MH087004 to S.A.S.; R21-DA29298 and R01-GM054508 to R.D.B. We thank M. Baxter for assistance with statistical analyses. We thank J. Feng, J.-W. Koo and C.-Y. Lu for technical assistance. We thank A. Suzuki and A. Arguello for comments on the manuscript. We thank R. Miller and the Center for Comparative Medicine and Surgery Facility at Mount Sinai School of Medicine for technical support.
Ana Garcia-Osta
Present address: Present address: CIMA, University of Navarra, CIBERNED, Pamplona 31008, Spain.,
Department of Neuroscience, Mount Sinai School of Medicine, New York, 10029, New York, USA
Dillon Y. Chen, Sarah A. Stern, Ana Garcia-Osta, Gabriella Pollonini, Dhananjay Bambah-Mukku & Cristina M. Alberini
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, 10029, New York, USA
Bernadette Saunier-Rebori & Robert D. Blitzer
Department of Psychiatry, Mount Sinai School of Medicine, New York, 10029, New York, USA
Robert D. Blitzer & Cristina M. Alberini
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D.Y.C., A.G.-O. and C.M.A. designed and developed this study. D.Y.C., S.A.S. and A.G.-O. carried out the behavioural studies. D.Y.C., A.G.-O., G.P. and D.B.-M. carried out the biochemical studies and analyses. R.D.B. and B.S.-R. designed and conducted the electrophysiology experiments. D.Y.C. and C.M.A. wrote the manuscript.
Correspondence to Cristina M. Alberini.
Patent pending on IGF-II as a strategy to enhance memory.
The file contains Supplementary Figures 1-12 with legends and Supplementary Tables 1-6. This file was replaced on 17 October 2011. (PDF 612 kb)
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Chen, D., Stern, S., Garcia-Osta, A. et al. A critical role for IGF-II in memory consolidation and enhancement. Nature 469, 491–497 (2011). https://doi.org/10.1038/nature09667
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Received: 20 August 2010
Accepted: 15 November 2010
Published: 26 January 2011
Issue Date: 27 January 2011
DOI: https://doi.org/10.1038/nature09667
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An understanding of the mechanisms of memory enhancement is vital for broadening our knowledge of memory processes, as well as for potential clinical applications. Yet very little is known about it. Experiments in rats now show that the administration of insulin-like growth factor II (IGF-II), a protein typically implicated in somatic tissue growth and repair, significantly enhances memory retention, promotes the memory proxy known as long-term potentiation and prevents forgetting. IGF-II acts by initiating a network of signalling cascades that can lead to synaptic potentiation and are most effective within a short time frame immediately following learning. IGF-II is therefore a potential target for modulating cognitive enhancement.
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