Research reportMelatonin ameliorates cognitive impairment induced by sleep deprivation in rats: Role of oxidative stress, BDNF and CaMKII

- Melatonin prevents cognitive impairment induced by sleep deprivation.
- Oxidative stress is reduced by melatonin in rats caused by sleep deprivation.
- Melatonin increases CaMKII and BDNF in cortex and hippocampus after sleep deprivation.

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.

This paper demonstrates that melatonin treatment prevents sleep deprivation-induced cognitive impairment in rats. The open field test and the Morris water maze are used to evaluate the cognitive impairment. Total movement distance (TMD) and faster movement time (FMT) are analyzed as a measure of excitability behavior. The distance to the center (DTC) and inner toriod time (ITT) are used as exploratory behavior. The results show that melatonin ameliorates cognitive impairment significantly. The possible mechanism may be involved in the oxidative stress, BDNF and CaMKII in cerebral cortex and hippocampus.138