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Uhrf2 deletion impairs the formation of hippocampus-dependent memory by changing the structure of the dentate gyrus

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Abstract

Ubiquitin-like with PHD and ring finger domains 2 (Uhrf2) is distributed in many brain regions, including the cortex and hippocampus. Decreased Uhrf2 expression is involved in neurodegenerative disease. A recent study showed Uhrf2 deletion impaired spatial memory; however, the mechanism remains elusive. In our study, we determined that Uhrf2+/− and Uhrf2−/− mice had significant learning and memory deficiencies in contextual fear conditioning (CFC) and the novel place recognition test but not in the novel object recognition test. Interestingly, there were no changes in the Uhrf2 protein levels in the hippocampus of C57BL6 mice after CFC training, which suggests Uhrf2 in adult mice may not be related to the formation of CFC long-term memory. Based on Nissl staining, Uhrf2 deletion caused neuropathological changes specifically in the crest of the dentate gyrus (DG), such as cell swelling, a vague outline and confused boundary; however, no changes were identified in the medial prefrontal cortex (mPFC). Transmission electron microscope assay further indicated a series of abnormal ultrastructure changes in neurons and glia in the DG crest. These results suggested that Uhrf2 deletion selectively blocked the development of the DG crest and impaired hippocampus-dependent learning and memory. Our study will facilitate a better understanding of the role of Uhrf2 protein in the central nervous system.

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Acknowledgements

This work is supported by the National Natural Science Foundation of China (Grant Numbers: 31571100, 91432306), Shandong Province Natural Science Foundation [grant number: ZR2014CM036] and the Fundamental Research Funds of Shandong University.

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  1. Xiao-Rong Chen and Shi-Cheng Sun contributed equally to this work.

Authors and Affiliations

  1. Shandong Provincial Key Laboratory of Mental Disorders, Department of Cell and Neurobiology, School of Basic Medicine, Shandong University, No. 44 Wenhua Xi Road, Jinan, 250012, Shandong, People’s Republic of China

    Xiao-Rong Chen, Shi-Cheng Sun, Shuai-Wen Teng, Yi-Fan Bie, Hui Yu, Zhe-Yu Chen & Yue Wang

  2. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, People’s Republic of China

    Liang Li & Da-Li Li

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  1. Xiao-Rong Chen
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Chen, XR., Sun, SC., Teng, SW. et al. Uhrf2 deletion impairs the formation of hippocampus-dependent memory by changing the structure of the dentate gyrus. Brain Struct Funct 223, 609–618 (2018). https://doi.org/10.1007/s00429-017-1512-1

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