title: The potential role of melatonin on sleep deprivation-induced cognitive impairments: implication of FMRP on cognitive function.
abstract: While prolonged sleep deprivation (SD) could lead to profound negative health consequences, such as impairments in vital biological functions of immunity and cognition, melatonin possesses powerful ameliorating effects against those harmful insults. Melatonin has strong antioxidant and anti-inflammatory effects that help to restore body's immune and cognitive functions. In this study, we investigated the possible role of melatonin in reversing cognitive dysfunction induced by SD in rats. Our experimental results revealed that sleep-deprived animals exhibited spatial memory impairment in the Morris water maze tasks compared with the control groups. Furthermore, there was an increased glial activation most prominent in the hippocampal region of the SD group compared to the normal control (NC) group. Additionally, markers of oxidative stress such as 4-hydroxynonenal (4-HNE) and 7,8-dihydro-8-oxo-deoxyguanine (8-oxo-dG) were significantly increased, while fragile X-mental retardation protein (FMRP) expression was decreased in the SD group. Interestingly, melatonin treatment normalized these events to control levels following SD. Our data demonstrate that SD induces oxidative stress through glial activation and decreases FMRP expression in the neurons. Furthermore, our results suggest the efficacy of melatonin for the treatment of sleep-related neuronal dysfunction, which occurs in neurological disorders such as Alzheimer's disease and autism.
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; Department of Neurology, Konkuk University Medical Center, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: K J
authors.initials: KJ
authors.lastname: Kwon
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: M K
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Jeon
authors.affiliation: Department of Biomedical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: C Y
authors.initials: CY
authors.lastname: Shin
authors.affiliation: Department of Neuroscience, Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea; Department of Neurology, Konkuk University Medical Center, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: alzdoc@naver.com.
authors.forename: S-H
authors.initials: SH
authors.lastname: Han
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000627:therapeutic use*; D008569:Memory Disorders / Q000209:etiology* / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012892:Sleep Deprivation / Q000150:complications*
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes; D000975:Antioxidants; D003849:Deoxyguanosine; D051860:Fragile X Messenger Ribonucleoprotein 1; D008550:Melatonin; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C497685:Fmr1 protein, rat; C027576:4-hydroxy-2-nonenal
keywords: FMRP; glia; learning and memory; melatonin; oxidative stress; sleep deprivation