title: Melatonin Alleviates the Epilepsy-Associated Impairments in Hippocampal LTP and Spatial Learning Through Rescue of Surface GluR2 Expression at Hippocampal CA1 Synapses.
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.
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.|Department of Neurology, The Affiliated Guangren Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, 710004, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Jia
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. jiangwen@fmmu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis*; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018091:Receptors, AMPA; D008550:Melatonin; C104722:glutamate receptor ionotropic, AMPA 2
keywords: Cognitive dysfunction; Epilepsy; GluR2; Melatonin