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Maged1 Co-interacting with CREB Through a Hexapeptide Repeat Domain Regulates Learning and Memory in Mice

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Abstract

Maged1 is a member of the type II melanoma antigen (MAGE) family of proteins, which is highly conserved in the brain between mouse and human. Recently, Maged1 has been reported to be involved in depression and impaired sexual behavior. However, the role of Maged1 in learning and memory remains unknown. The aim of the present study was therefore to investigate whether Maged1 deficiency can impair learning and memory formation. By behavioral tests and electrophysiological recording, we observed that 5–6-month-old Maged1 knockout mice displayed the reduced basal synaptic transmission, pronounced hippocampal dysfunction, impaired spatial learning, and a deficit in long-term potentiation induction. Data from immunohistochemical and Western blot showed the reduced dendritic spine density and the number of synapses in the hippocampus of the Maged1 knockout mice, and Maged1 deficiency prevented the interaction of Maged1 with cAMP response element-binding protein (CREB). Furthermore, by chromatin immunoprecipitation and luciferase assay, we observed the downregulated activity of CREB and the suppressed CREB-dependent transcription after deficiency of Maged1, which lead to the decreased levels of brain-derived neurotrophic factor. Taken together, our results provide the evidence that Maged1 is involved in synaptic transmission and hippocampus-dependent learning and memory formation.

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Acknowledgments

We thank Dr. Ying Xu for kindly providing all kinds of plasmids of Maged1. This work is partially supported by the National Basic Research Program of China (2013CB835100, 2011CBA01104), National Natural Science Foundation of China (nos. 81222013 and 30871264), and Specialized Research Funds for the Doctoral Program of Higher Education (20070284042, 20110091120029) to J Gao. J-J Yang is supported by the National Natural Science Foundation of China (81271216) and A-L Xu by the National Natural Science Foundation of China (nos. 81200186 and 81171233) and Natural Science Foundation of Shandong (ZR2011BL026).

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Authors and Affiliations

  1. Model Animal Research Center and MOE Key Laboratory of Model Animals for Disease Study, Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 22 Hankou Road, Nanjing, 210093, Jiangsu, China

    JianJun Yang, BeiBei Lai, XiaoMin Li, MuHuo Ji, Xiang Gao & Jun Gao

  2. Department of Neurobiology and Department of Pharmacology, Key Laboratory for Neurodegenerative Disease of Jiangsu Province, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China

    Yu Liu, Gang Hu & Jun Gao

  3. Department of Physiology, Binzhou Medical College, Shandong, 264003, China

    AiLi Xu

  4. Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Zhejiang, 325035, China

    YongNa Zhao & WeiFeng Li

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  1. JianJun Yang
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  2. BeiBei Lai
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  10. Xiang Gao
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  11. Jun Gao
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Correspondence to Xiang Gao or Jun Gao.

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J. Yang, B. Lai, and A. Xu contributed equally to this work.

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Yang, J., Lai, B., Xu, A. et al. Maged1 Co-interacting with CREB Through a Hexapeptide Repeat Domain Regulates Learning and Memory in Mice. Mol Neurobiol 51, 8–18 (2015). https://doi.org/10.1007/s12035-014-8677-x

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  • DOI: https://doi.org/10.1007/s12035-014-8677-x

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