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: 41.46). 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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Available from: Sarah Stern, Apr 11, 2014
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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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    ABSTRACT: Recent work has reported that the insulin-like growth factor 2 (IGF2) promotes memory enhancement. Furthermore, impaired insulin or IGF1 functions have been suggested to play a role in the pathogenesis of neurodegeneration and cognitive impairments, hence implicating the insulin/IGF system as an important target for cognitive enhancement and/or the development of novel treatments against cognitive disorders. Here, we tested the effect of intracerebral injections of IGF1, IGF2, or insulin on memory consolidation and persistence in rats. We found that a bilateral injection of insulin into the dorsal hippocampus transiently enhances hippocampal-dependent memory and an injection of IGF1 has no effect. None of the three peptides injected into the amygdala affected memories critically engaging this region. Together with previous data on IGF2, these results indicate that IGF2 produces the most potent and persistent effect as a memory enhancer on hippocampal-dependent memories. We suggest that the memory-enhancing effects of insulin and IGF2 are likely mediated by distinct mechanisms.
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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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