PMID- 23933144 OWN - NLM STAT- MEDLINE DCOM- 20141218 LR - 20131101 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 256 DP - 2013 Nov 1 TI - Melatonin ameliorates cognitive impairment induced by sleep deprivation in rats: role of oxidative stress, BDNF and CaMKII. PG - 72-81 LID - S0166-4328(13)00463-4 [pii] LID - 10.1016/j.bbr.2013.07.051 [doi] AB - Sleep deprivation (SD) has been shown to induce oxidative stress which causes cognitive impairment. Melatonin, an endogenous potent antioxidant, protects neurons from oxidative stress in many disease models. The present study investigated the effect of melatonin against SD-induced cognitive impairment and attempted to define the possible mechanisms involved. SD was induced in rats using modified multiple platform model. Melatonin (15 mg/kg) was administered to the rats via intraperitoneal injection. The open field test and Morris water maze were used to evaluate cognitive ability. The cerebral cortex (CC) and hippocampus were dissected and homogenized. Nitric oxide (NO) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) enzyme activity of hippocampal and cortical tissues (10% wet weight per volume) were performed to determine the level of oxidative stress. The expression of brain-derived neurotrophic factor (BDNF) and calcium-calmodulin dependent kinase II (CaMKII) proteins in CC and hippocampus was assayed by means of immunohistochemistry. The results revealed that SD impairs cognitive ability, while melatonin treatment prevented these changes. In addition, melatonin reversed SD-induced changes in NO, MDA and SOD in both of the CC and hippocampus. The results of immunoreactivity showed that SD decreased gray values of BDNF and CaMKII in CC and hippocamal CA1, CA3 and dentate gyrus regions, whereas melatonin improved the gray values. In conclusion, our results suggest that melatonin prevents cognitive impairment induced by SD. The possible mechanism may be attributed to its ability to reduce oxidative stress and increase the levels of CaMKII and BDNF in CC and hippocampus. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Zhang, Lei AU - Zhang L AD - Experiment Teaching Center of Basic Medicine, The Fourth Military Medical University, Xi'an, 710033 Shan Xi Province, China; Department of General Surgery, 406 Hospital, Da Lian, 116041 Liao Ning Province, China; State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, 710033 Shan Xi Province, China. FAU - Zhang, Hu-Qin AU - Zhang HQ FAU - Liang, Xiang-Yan AU - Liang XY FAU - Zhang, Hai-Feng AU - Zhang HF FAU - Zhang, Ting AU - Zhang T FAU - Liu, Fang-E AU - Liu FE LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130806 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nootropic Agents) RN - 31C4KY9ESH (Nitric Oxide) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - JL5DK93RCL (Melatonin) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Brain/*drug effects/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism MH - Cerebral Cortex/drug effects/metabolism MH - Cognition Disorders/*drug therapy/*etiology/metabolism MH - Hippocampus/drug effects/metabolism MH - Immunohistochemistry MH - Male MH - Malondialdehyde/metabolism MH - Maze Learning/drug effects/physiology MH - Melatonin/*pharmacology MH - Nitric Oxide/metabolism MH - Nootropic Agents/*pharmacology MH - Oxidative Stress/drug effects/physiology MH - Rats, Sprague-Dawley MH - Sleep Deprivation/*complications MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - BDNF OT - CC OT - CG OT - CaMKII OT - Calcium-calmodulin dependent kinase II OT - Cognitive impairment OT - DG OT - DTC OT - EL OT - FMT OT - ITT OT - LTP OT - MDA OT - MSD(1) OT - MSD(2) OT - Melatonin OT - NCP OT - NO OT - OF OT - Oxidative stress OT - P-CaMKII OT - PBS OT - REM OT - ROS OT - SD OT - SD(1) OT - SD(2) OT - SOD OT - Sleep deprivation OT - TMD OT - WPG(1) OT - WPG(2) OT - brain-derived neurotrophic factor OT - cerebral cortex OT - control group OT - dentate gyrus OT - distance to the center OT - escape latency OT - faster movement time OT - inner toriod time OT - long-term potentiation OT - malondialdehyde OT - melatonin with sleep deprivation 2 OT - melatonin with sleep deprivation group 1 OT - nitric oxide OT - number of crossings over the former platform location OT - open field OT - phosphate buffer saline OT - phosphorylated Calcium-calmodulin dependent kinase II OT - rapid eye movent OT - reactive oxygen species OT - sleep deprivation OT - sleep deprivation 2 OT - sleep deprivation group 1 OT - superoxide dismutase OT - total movement distance OT - wide platform group 1 OT - wide platform group 2 EDAT- 2013/08/13 06:00 MHDA- 2014/12/19 06:00 CRDT- 2013/08/13 06:00 PHST- 2013/06/22 00:00 [received] PHST- 2013/07/23 00:00 [revised] PHST- 2013/07/27 00:00 [accepted] PHST- 2013/08/13 06:00 [entrez] PHST- 2013/08/13 06:00 [pubmed] PHST- 2014/12/19 06:00 [medline] AID - S0166-4328(13)00463-4 [pii] AID - 10.1016/j.bbr.2013.07.051 [doi] PST - ppublish SO - Behav Brain Res. 2013 Nov 1;256:72-81. doi: 10.1016/j.bbr.2013.07.051. Epub 2013 Aug 6.