A critical role for IGF-II in memory consolidation and enhancement

Dillon Y. Chen, Sarah A. Stern, Ana Garcia-Osta, Bernadette Saunier-Rebori, Gabriella Pollonini, Dhananjay Bambah-Mukku, Robert D. Blitzer, Cristina M. Alberini

Research output: Contribution to journalArticle

Abstract

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 2 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 2 and increased expression of GluR1 (also known as GRIA1) β ±-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.

Original languageEnglish (US)
Pages (from-to)491-499
Number of pages9
JournalNature
Volume469
Issue number7331
DOIs
StatePublished - Jan 27 2011

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ASJC Scopus subject areas

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Cite this

Chen, D. Y., Stern, S. A., Garcia-Osta, A., Saunier-Rebori, B., Pollonini, G., Bambah-Mukku, D., Blitzer, R. D., & Alberini, C. M. (2011). A critical role for IGF-II in memory consolidation and enhancement. Nature, 469(7331), 491-499. https://doi.org/10.1038/nature09667