Editors' ChoiceMemory

Growth Factor Makes Memories Stick

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Science Translational Medicine  16 Feb 2011:
Vol. 3, Issue 70, pp. 70ec20
DOI: 10.1126/scitranslmed.3002209

We all wish that there were a magic pill to strengthen our memories. But for scientists to discover such a pill, they first need to better understand the molecular mechanisms involved in memory consolidation, the process through which newly learned information sticks in the mind. Now, Chen et al. show that brain administration of insulin-like growth factor II (IGF-II), a protein involved in growth and metabolism, prevents forgetting by enhancing long-term potentiation and memory retention.

The transcription factors adenosine 3´,5´-monophosphate (cAMP) response element–binding protein (CREB) and CCAAT enhancer–binding protein (C/EBP) are known to play critical roles in memory consolidation, and their activities correlate with synaptic changes, which represent the neuroanatomical basis of memory. In a previous study, the authors found that within 6 to 9 hours after the learning of new information, C/EBPβ is activated. Because the IGF-II gene is a transcriptional target of C/EBPβ, the authors tested whether IGF-II expression was increased during memory formation, and indeed, it was.

The ability of IGF-II to enhance memory was temporally restricted to a time window of 24 hours after either learning something new or after memory retrieval. The authors then used a combination of specific inhibitors of the IGF-II receptor or knocked down production of the receptor protein so as to show that the observed effects were mediated specifically through the IGF-II receptor and not through other IGF or the insulin receptor(s), which IGF-II can also activate. IGF-II–mediated memory enhancement did not require C/EBPβ but was accompanied by an increase in the activation of synaptic glycogen synthase kinase 3 beta (GSK3β). Known to be involved in long-term potentiation, GSK3β activation may account for the increase in concentrations of glutamate receptor 1 protein in synapses during memory boosting. Thus, these studies define a previously unknown role for IGF-II and the IGF-II receptor in the brain and raise the possibility that IGF-II represents a novel target for cognitive enhancement therapies.

D. Y. Chen et al., A critical role for IGF-II in memory consolidation and enhancement. Nature 469, 491–497 (2011). [Abstract]

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