Melatonin Attenuates Scopolamine-Induced Memory/Synaptic Disorder by Rescuing EPACs/miR-124/Egr1 Pathway
- 1.5k Downloads
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.
KeywordsMelatonin EPAC miR-124 Synaptic disorder Dendritic spine
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).
- 4.Ramirez-Rodriguez G, Ortiz-Lopez L, Dominguez-Alonso A, Benitez-King GA, Kempermann G (2010) Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice. J Pineal Res 50:29–37. doi: 10.1111/j.1600-079X.2010.00802.x PubMedCrossRefGoogle Scholar
- 6.Gonzalez-Burgos I, Letechipia-Vallejo G, Lopez-Loeza E, Morali G, Cervantes M (2007) Long-term study of dendritic spines from hippocampal CA1 pyramidal cells, after neuroprotective melatonin treatment following global cerebral ischemia in rats. Neurosci Lett 423:162–166. doi: 10.1016/j.neulet.2007.06.050 PubMedCrossRefGoogle Scholar
- 34.Clokie SJ, Lau P, Kim HH, Coon SL, Klein D (2012) Micro RNAs in the pineal gland: mir-483 regulates melatonin synthesis by targeting arylalkylamine N-acetyltransferase. J Biol Chem. doi: 10.1074/jbc.M112.356733
- 36.Jeong JK, Moon MH, Lee YJ, Seol JW, Park SY (2012) Melatonin-induced autophagy protects against human prion protein-mediated neurotoxicity. J Pineal Res. doi: 10.1111/j.1600-079X.2012.00980.x