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


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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    • "However, interestingly, compared to most tissues, Igf2 expression remains relatively elevated in the adult brain [12] [15], where its function has only recently started to be unraveled. Chen et al. (2011) showed that IGF2 in the adult rat hippocampus is upregulated after learning and required for memory consolidation [16]. Moreover , administration of recombinant IGF2 with learning or memory reactivation significantly enhances several types of hippocampal-dependent memories [16] [17] and fear extinction [17] [18], suggesting that IGF2 acts as a potent memory or cognitive enhancer. "
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    ABSTRACT: Insulin like growth factor 2 (Igf2) is known as a maternally imprinted gene involved in growth and development. Recently, Igf2 was found to also be regulated and required in the adult rat hippocampus for long-term memory formation, raising the question of its allelic regulation in adult brain regions following experience and in cognitive processes. We show that, in adult rats, Igf2 is abundantly expressed in brain regions involved in cognitive functions, like hippocampus and prefrontal cortex, compared to the peripheral tissues. In contrast to its maternal imprinting in peripheral tissues, Igf2 is mainly expressed from the maternal allele in these brain regions. The training-dependent increase in Igf2 expression derives proportionally from both parental alleles, and, hence, is mostly maternal. Thus, Igf2 parental expression in the adult rat brain does not follow the imprinting rules found in peripheral tissues, suggesting differential expression regulation and functions of imprinted genes in the brain.
    PLoS ONE 10/2015; 10(10):e0141078. DOI:10.1371/journal.pone.0141078 · 3.23 Impact Factor
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    • "There are several lines of evidence for resistance to IR/IGF1R signaling in AD neurons [8, 11, 14–16] whereas there are few data in terms of IGF2R actions in AD. However, in an experimental study by Chen et al. [18], IGF2R signaling was of major importance for memory consolidation [18]. In the human AD brain, IGF-II expression was reduced [21], and the expression of IGF-II and IGF2R as well as IGF2R binding decreased with advancing disease [14] [15]. "
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    ABSTRACT: Background: Insulin-like growth factor-II (IGF-II) is important for brain development. Although IGF-II is abundant also in adult life, little is known of the role of IGF-II in Alzheimer's disease (AD). Objective and methods: This was a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 32), stable MCI (SMCI, n = 13), or other dementias (n = 15). IGF-II, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 were analyzed in serum and cerebrospinal fluid (CSF). Results: Levels of IGF-II, IGFBP-1, and IGFBP-2 were similar in all groups in the total study population. Gender-specific analyses showed that in men (n = 40), CSF IGF-II level was higher in AD compared to SMCI and controls (p < 0.01 and p < 0.05, respectively). Furthermore, CSF IGFBP-2 level was increased in AD men versus SMCI men (p < 0.01) and tended to be increased versus control men (p = 0.09). There were no between-group differences in women (n = 40). In the total study population (n = 80) as well as in men (n = 40), CSF levels of IGF-II and IGFBP-2 correlated positively with CSF levels of the AD biomarkers total-tau and phosphorylated tau protein. Conclusion: In men, but not women, in the early stages of AD, CSF IGF-II level was elevated, and CSF IGFBP-2 level tended to be increased, compared to healthy controls.
    Journal of Alzheimer's disease: JAD 09/2015; 48(3). DOI:10.3233/JAD-150351 · 4.15 Impact Factor
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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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