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Molecular Neurobiology

, Volume 47, Issue 1, pp 373–381 | Cite as

Melatonin Attenuates Scopolamine-Induced Memory/Synaptic Disorder by Rescuing EPACs/miR-124/Egr1 Pathway

  • Xiong Wang
  • Zhi-Hao Wang
  • Yuan-Yuan Wu
  • Hui Tang
  • Lu Tan
  • Xiang Wang
  • Xin-Ya Gao
  • Yan-Si Xiong
  • Dan LiuEmail author
  • Jian-Zhi Wang
  • Ling-Qiang ZhuEmail author
Article

Abstract

Alzheimer’s disease (AD) is the most prevalent type of dementia in elderly people. There are decreased melatonin levels in the serum of AD patients, and melatonin supplements are able to reverse AD pathology and memory deficits in many animal experiments and clinical trials. However, the underlying mechanism regarding how melatonin rescues the AD-like memory/synaptic disorder remains unknown. Here, we use the Morris water maze, step-down inhibitory avoidance task, in vivo long-term potentiation recording, and Golgi staining and report that intraperitoneal injection of melatonin (1 mg/kg/day) for 14 days in rats effectively reverses the memory and synaptic impairment in scopolamine-induced amnesia, a well-recognized dementia animal model. Using real-time polymerase chain reaction and western blotting experiments, we further determined that melatonin rescues the EPACs/miR-124/Egr1 signal pathway, which is important in learning and memory, as reported recently. Our studies provide a novel underlying epigenetic mechanism for melatonin to attenuate the synaptic disorder and could benefit drug discovery in neurodegenerative diseases.

Keywords

Melatonin EPAC miR-124 Synaptic disorder Dendritic spine 

Notes

Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (30971478, 91132725, 31201011), the New Century Excellent Talent of Education Ministry (NCET-10-0421), the Ministry of Science and Technology of China (2011DFG33250), the New Investigator Research Grant of Alzheimer’s Association (NIRG-11-205737), and the Fundamental Research Funds for the Central Universities, HUST, (nos. 0118510011 and 0118510019).

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Xiong Wang
    • 1
  • Zhi-Hao Wang
    • 1
  • Yuan-Yuan Wu
    • 1
  • Hui Tang
    • 1
  • Lu Tan
    • 1
  • Xiang Wang
    • 1
  • Xin-Ya Gao
    • 1
  • Yan-Si Xiong
    • 1
  • Dan Liu
    • 2
    • 3
    Email author
  • Jian-Zhi Wang
    • 1
    • 3
  • Ling-Qiang Zhu
    • 1
    • 3
    Email author
  1. 1.Department of Pathophysiology, Key Laboratory of Neurological Diseases of Education Committee of China, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.Department of Genetics, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  3. 3.Key Laboratory of Neurological DiseasesMinistry of EducationWuhanChina

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