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Melatonin Alleviates the Epilepsy-Associated Impairments in Hippocampal LTP and Spatial Learning Through Rescue of Surface GluR2 Expression at Hippocampal CA1 Synapses

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Abstract

Epilepsy-associated cognitive impairment is common, and negatively impacts patients’ quality of life. However, most antiepileptic drugs focus on the suppression of seizures, and fewer emphasize treatment of cognitive dysfunction. Melatonin, an indolamine synthesized primarily in the pineal grand, is reported to be neuroprotective against several central nervous system disorders. In this study, we investigated whether melatonin could reverse cognitive dysfunction in lithium-pilocarpine treated rats. Chronic treatment with melatonin (8 mg/kg daily for 15 days) after induction of status epilepticus significantly alleviated seizure severity, reduced neuronal death in the CA1 region of the hippocampus, improved spatial learning (as measured by the Morris water maze test), and reversed LTP impairments, compared to vehicle treatment. Furthermore, we found that melatonin rescued the decreased surface levels of GluR2 in the CA1 region observed in epilepsy, which might be the underlying mechanism of the neuroprotective and synapse-modulating function of melatonin. Our study provides experimental evidence for the possible clinical utility of melatonin as an adjunctive therapy to prevent epilepsy-associated cognitive impairments.

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Acknowledgements

This work was supported by Grants from the National Science Foundation of China (Grant Numbers 81271432 and 81571262). The funders played no role in study design, data collection and analysis, the decision to publish, or preparation of the manuscript.

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    1. Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

      Yue Ma, Xiaolong Sun, Juan Li, Ruihua Jia, Fang Yuan, Dong Wei & Wen Jiang

    2. Department of Neurology, The Affiliated Guangren Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, 710004, People’s Republic of China

      Juan Li

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    1. Yue Ma
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    Yue Ma and Xiaolong Sun have contributed equally to this study.

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    Ma, Y., Sun, X., Li, J. et al. Melatonin Alleviates the Epilepsy-Associated Impairments in Hippocampal LTP and Spatial Learning Through Rescue of Surface GluR2 Expression at Hippocampal CA1 Synapses. Neurochem Res 42, 1438–1448 (2017). https://doi.org/10.1007/s11064-017-2200-5

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