Melatonin preserves longevity protein (sirtuin 1) expression in the hippocampus of total sleep-deprived rats
Melatonin preserves longevity protein (sirtuin 1) expression in the hippocampus of total sleep-deprived rats
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DOI：
10.1111/j.1600-079x.2009.00704.x
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发表时间：
2009-10-01
影响因子：
10.3
通讯作者：
Lan, Chyn-Tair
中科院分区：
文献类型：
--
作者：
Chang, Hung-Ming;Wu, Un-In;Lan, Chyn-Tair
睡眠障碍导致认知功能障碍，其中海马中受损的神经元可塑性可能强调了这种缺陷的分子机制。由于sirtuin 1（SIRT 1）在维持代谢稳态和神经元可塑性方面起着重要作用，本研究旨在确定褪黑激素是否对完全睡眠剥夺（TSD）后保持SIRT 1激活发挥有益作用。通过水盘法连续5天进行TSD。在此期间，动物每天接受剂量为5、25、50或100 mg/kg的褪黑激素。采用细胞色素氧化酶（考克斯）组织化学、SIRT 1免疫组织化学和Morris水迷宫学习实验，分别观察神经元可塑性的代谢、神经化学和行为学变化。结果表明：正常大鼠海马锥体细胞层和颗粒细胞层内均可见大量考克斯和SIRT 1阳性神经元，且染色强度较强。TSD后，考克斯和SIRT 1的反应性都急剧下降，如染色模式和标记频率降低所示。行为学数据与形态学结果一致，其中水迷宫空间记忆测试在TSD后显著受损。然而，在接受不同剂量褪黑激素的大鼠中，考克斯和SIRT 1的表达都被成功地保留。在行为测试中表现得相当好，进一步加强了褪黑激素的有益作用。这些研究结果表明，褪黑激素可能作为一种新的治疗策略，用于预防TSD导致的记忆缺陷，可能通过有效地保持代谢功能和神经元可塑性参与维持认知活动。
Sleep disorders cause cognitive dysfunction in which impaired neuronal plasticity in the hippocampus may underline the molecular mechanisms of this deficiency. As sirtuin 1 (SIRT1) plays an important role in maintaining metabolic homeostasis and neuronal plasticity, this study is aimed to determine whether melatonin exerts beneficial effects on preserving SIRT1 activation following total sleep deprivation (TSD). TSD was performed by disc on water method for five consecutive days. During this period, animals daily received melatonin at doses of 5, 25, 50 or 100 mg/kg. The cytochrome oxidase (COX) histochemistry, SIRT1 immunohistochemistry together with Morris water maze learning test were performed to examine the metabolic, neurochemical, as well as the behavioral changes in neuronal plasticity, respectively. The results indicate that in normal rats, numerous COX and SIRT1 positive-labeled neurons with strong staining intensities were found in hippocampal pyramidal and granular cell layers. Following TSD, both COX and SIRT1 reactivities were drastically decreased as revealed by reduced staining pattern and labeling frequency. Behavioral data corresponded well with morphological findings in which spatial memory test in water maze was significantly impaired after TSD. However, in rats receiving different doses of melatonin, both COX and SIRT1 expressions were successfully preserved. Considerably better performance on behavioral testing further strengthened the beneficial effects of melatonin. These findings suggest that melatonin may serve as a novel therapeutic strategy directed for preventing the memory deficits resulting from TSD, possibly by effectively preserving the metabolic function and neuronal plasticity engaged in maintaining cognitive activity.