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Volume 7 Supplement 1

Proceedings of the 2011 International Conference on Molecular Neurodegeneration

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

Molecular Neurodegeneration volume 7, Article number: O12 (2012) Cite this article

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.

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    Authors and Affiliations

    1. 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

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

    Authors
    1. Ying Yang
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    2. Xiaogang Shu
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    3. Dan Liu
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    4. Lei Pei
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    5. Lingqiang Zhu
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    6. Qing Tian
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    7. Jianzhi Wang
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    8. Youming Lu
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    Corresponding author

    Correspondence to Youming Lu.

    Additional information

    Ying Yang, Xiaogang Shu contributed equally to this work.

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    Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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    Cite this article

    Yang, Y., Shu, X., Liu, D. et al. EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268 translation. Mol Neurodegeneration 7 (Suppl 1), O12 (2012). https://doi.org/10.1186/1750-1326-7-S1-O12

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    • DOI: https://doi.org/10.1186/1750-1326-7-S1-O12

    Keywords

    Molecular Neurodegeneration

    ISSN: 1750-1326