This article is part of the supplement: Proceedings of the 2011 International Conference on Molecular Neurodegeneration

Open Access Oral presentation

EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268 translation

Ying Yang†, Xiaogang Shu†, Dan Liu, Lei Pei, Lingqiang Zhu, Qing Tian, Jianzhi Wang and Youming Lu*

Author Affiliations

Department of Pathophysiology, Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

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Molecular Neurodegeneration 2012, 7(Suppl 1):O12 doi:10.1186/1750-1326-7-S1-O12


The electronic version of this article is the complete one and can be found online at: http://www.molecularneurodegeneration.com/content/7/S1/O12


Published:7 February 2012

© 2012 Yang et al; licensee BioMed Central Ltd.

Background

EPAC proteins are the guanine nucleotide exchange factors that act as the intracellular receptors for cyclic AMP. Two variants of EPAC genes including EPAC1 and EPAC2 are found to be expressed throughout the brain. But, their neurological functions have yet to be described.

Method

We generate genetically-modified strains of mice with deficiency in expression of EPAC1 (EPAC1-/- mice), or EPAC2 (EPAC2-/- mice) or both EPAC1 and EPAC2 genes (EPAC-/- mice).

Result and conclusion

We show that EPAC null mutation in the forebrain of mice impairs LTP of synaptic transmission that is paralleled with the abnormal spatial learning and social behaviors. This impairment is mediated in a direct manner by expressing miR-124, which binds to and inhibits Zif268 mRNA translation. Knockdown of miR-124 completely reverses the phenotypes observed in EPAC-/- mice, whereas over-expression of miR-124 mimics EPAC null mutation. Thus, miR-124 constitutes a critical epigenetic signaling downstream of EPAC proteins for regulation of learning and social interactions.