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

Author

Listed:
  • Dillon Y. Chen

    (Mount Sinai School of Medicine)

  • Sarah A. Stern

    (Mount Sinai School of Medicine)

  • Ana Garcia-Osta

    (Mount Sinai School of Medicine
    Present address: CIMA, University of Navarra, CIBERNED, Pamplona 31008, Spain.)

  • Bernadette Saunier-Rebori

    (Mount Sinai School of Medicine)

  • Gabriella Pollonini

    (Mount Sinai School of Medicine)

  • Dhananjay Bambah-Mukku

    (Mount Sinai School of Medicine)

  • Robert D. Blitzer

    (Mount Sinai School of Medicine
    Mount Sinai School of Medicine)

  • Cristina M. Alberini

    (Mount Sinai School of Medicine
    Mount Sinai School of Medicine)

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 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.

Suggested Citation

  • Dillon Y. Chen & Sarah A. Stern & Ana Garcia-Osta & Bernadette Saunier-Rebori & Gabriella Pollonini & Dhananjay Bambah-Mukku & Robert D. Blitzer & Cristina M. Alberini, 2011. "A critical role for IGF-II in memory consolidation and enhancement," Nature, Nature, vol. 469(7331), pages 491-497, January.
    • Handle: RePEc:nat:nature:v:469:y:2011:i:7331:d:10.1038_nature09667
    DOI: 10.1038/nature09667
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    Cited by:

    1. Raihan K Uddin & Shiva M Singh, 2013. "Hippocampal Gene Expression Meta-Analysis Identifies Aging and Age-Associated Spatial Learning Impairment (ASLI) Genes and Pathways," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-16, July.
    2. James K Bursley & Adrian Nestor & Michael J Tarr & J David Creswell, 2016. "Awake, Offline Processing during Associative Learning," PLOS ONE, Public Library of Science, vol. 11(4), pages 1-15, April.

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