title: A critical role for IGF-II in memory consolidation and enhancement.
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.
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Dillon Y
authors.initials: DY
authors.lastname: Chen
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Stern
authors.forename: Ana
authors.initials: A
authors.lastname: Garcia-Osta
authors.forename: Bernadette
authors.initials: B
authors.lastname: Saunier-Rebori
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pollonini
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Bambah-Mukku
authors.forename: Robert D
authors.initials: RD
authors.lastname: Blitzer
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Alberini
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism* / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D007335:Insulin-Like Growth Factor II