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

Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
Nature (Impact Factor: 42.35). 01/2011; 469(7331):491-7. DOI: 10.1038/nature09667
Source: PubMed

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.

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    • "has recently been reported to be involved in dendritic plasticity and memory consolidation and enhancement (Agis-Balboa et al, 2011; Chen et al, 2011; Schmeisser et al, 2012). Thus, we hypothesized that the dendritic retraction and anxiety-like behavior may be closely associated with IGF-2 signaling. "
    Dataset: npp2014128a
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    • "Hence BLA injections of insulin have no effect on hippocampal-or amygdala-dependent memories. IGF1 injected into the hippocampus does not affect hippocampal-or amygdala-dependent memories We have previously found that a bilateral hippocampal injection of IGF1 has no effect on IA memory retention (Chen et al. 2011). "
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    • "Indeed, single-cell PCR reveals that insulin is strongly expressed in GABAergic neurogliaform cells in the cerebral cortex (71). Similarly, insulin-like growth factor-1 (IGF-1), IGF-2, and their receptors exist in the CNS (72–75). When insulin binds to the insulin receptor, IRS-1 and -2 (insulin receptor substrate) undergo tyrosine phosphorylation and bind phosphatidylinositol 3-kinase (PI3K) (76), which activates AKT and glycogen-synthase kinase-3β (GSK3β) (77–79). "
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