TY - JOUR
T1 - A critical role for IGF-II in memory consolidation and enhancement
AU - Chen, Dillon Y.
AU - Stern, Sarah A.
AU - Garcia-Osta, Ana
AU - Saunier-Rebori, Bernadette
AU - Pollonini, Gabriella
AU - Bambah-Mukku, Dhananjay
AU - Blitzer, Robert D.
AU - Alberini, Cristina M.
PY - 2011/1/27
Y1 - 2011/1/27
N2 - 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 2 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 2 and increased expression of GluR1 (also known as GRIA1) β ±-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.
AB - 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 2 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 2 and increased expression of GluR1 (also known as GRIA1) β ±-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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U2 - 10.1038/nature09667
DO - 10.1038/nature09667
M3 - Article
C2 - 21270887
AN - SCOPUS:79251578040
SN - 0028-0836
VL - 469
SP - 491
EP - 499
JO - Nature
JF - Nature
IS - 7331
ER -