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

Article

关键词: GROWTH-FACTOR-II;    LONG-TERM POTENTIATION;    PROTEIN-SYNTHESIS;    BINDING-PROTEIN;    PERSISTENT DISRUPTION;    RAT HIPPOCAMPUS;    RECONSOLIDATION;    RECEPTOR;    GENE;    MECHANISMS;   

DOI  :  10.1038/nature09667

来源: SCIE

【 摘 要 】

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 beta 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 GSK3 beta and increased expression of GluR1 (also known as GRIA1) alpha-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.

【 授权许可】

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