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Inhibition of miR-219 Alleviates Arsenic-Induced Learning and Memory Impairments and Synaptic Damage Through Up-regulating CaMKII in the Hippocampus

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Abstract

Epidemiological investigations and experimental studies indicate that chronic arsenic exposure can reduce learning and memory function. However, the underlying mechanism of this effect remains largely unknown. Emerging evidence suggests that microRNA (miRNA) play an important role in toxicant exposure and a regulatory role in cognitive function. In this study, we observed that subchronic arsenic exposure induced impairment of learning and memory and significantly up-regulated miRNA-219 (miR-219) expression in the mouse hippocampus. Furthermore, the expression of CaMKII, an experimentally validated target of miR-219, was decreased in the mice exposed to arsenic. Suppression of miR-219 by adeno-associated viral (AAV)-delivered anti-miR-219 prevented the arsenic-induced impairment of learning and memory and relieved the pathological changes in the synaptic structure of the hippocampus. Furthermore, we observed that the NMDA receptor subunit 2 (NR2) and the memory-related proteins c-Fos and c-Jun were up-regulated by inhibition of miR-219 in the mouse hippocampus. Taken together, the results of this study indicate that inhibition of miR-219 regulates arsenic-induced damage in the structure of the hippocampus and impairment of learning and memory, possibly by targeting CaMKII. Suppression of miR-219 may be a potential strategy to ameliorate arsenic-induced neurotoxicity.

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Acknowledgements

This work was supported by the Basic Research Projects of Colleges and Universities of Liaoning Province, China (LQ2017037).

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    Authors and Affiliations

    1. Department of Occupational and Environmental Health, Dalian Medical University, Dalian, 116044, People’s Republic of China

      Dunjia Wang, Xiaoxia Shi & Fengyuan Piao

    2. Digestive Endoscopic Department of the second Hospital of Jilin University, Changchun, 130000, People’s Republic of China

      Xiaodong Wang

    3. 3Department of Food Nutrition and Safety, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China

      Xiaofang Liu, Guang Yang & Cong Zhang

    4. 4Preventive Medicine Laboratory, School of Public Health, Dalian Medical University, Dalian, 116044, People’s Republic of China

      Liping Jiang

    5. Liaoning Anti-Degenerative Diseases Natural Products Engineering Research Center, Dalian Medical University, Dalian, 116044, People’s Republic of China

      Liping Jiang

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    1. Dunjia Wang
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    Correspondence to Cong Zhang.

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    Dunjia Wang, Xiaodong Wang, Cong Zhang and Fengyuan Piao have contributed equally to this work.

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    Wang, D., Wang, X., Liu, X. et al. Inhibition of miR-219 Alleviates Arsenic-Induced Learning and Memory Impairments and Synaptic Damage Through Up-regulating CaMKII in the Hippocampus. Neurochem Res 43, 948–958 (2018). https://doi.org/10.1007/s11064-018-2500-4

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