Zhang Lei, Guo Hong-Liang, Zhang Hu-Qin, Xu Tian-Qi, He Bing, Wang Zhen-Hai, Yang Yi-Peng, Tang Xiao-Dan, Zhang Peng, Liu Fang-E
Medical College, Xi'an Peihua UniversityXi'an, Shaanxi Province, China.
Department of General Surgery, 406 Hospital of PLADalian, Liaoning, China.
Am J Transl Res. 2017 May 15;9(5):2231-2242. eCollection 2017.
Sleep deprivation (SD) has been shown to induce anxiety-like behavior. Melatonin, an endogenous potent antioxidant, protects neurons from oxidative stress in many disease models. Here we investigated the effect of melatonin against SD-induced anxiety-like behavior 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 elevated plus maze test, open field test and light-dark exploration were used to evaluate anxiety-like behavior. Serum corticosterone was measured to determine stress level. Malondialdehyde (MDA) level and superoxide dismutase (SOD) enzyme activity of amygdala and serum were performed to determine the level of oxidative stress. Levels of protein were detected by means of Western blot. The results showed that SD induces anxiety-like behavior, while melatonin treatment prevented these changes. Serum corticosterone also increased with SD but its levels were normalized by melatonin. In addition, melatonin reversed SD-induced changes in MDA and SOD in both of amygdala and serum. The results of Western blot showed that melatonin attenuated the up-regulation of NR2B-containing N-methyl-D-aspartate receptors, GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor as well as phosphorylation of GluR1 at Ser831, and Ca/calmodulin-dependent protein kinase II-alpha in SD rats. Meanwhile, melatonin blocked the down-regulation of γ-aminobutyric acid A-alpha-2 receptor. In conclusion, our results suggest that melatonin prevents anxiety-like behavior induced by SD. The possible mechanism may be attributed to its ability to reduce oxidative stress and maintain balance between GABAergic and glutamatergic transmission.
睡眠剥夺（SD）已被证明会诱发焦虑样行为。褪黑素是一种内源性强效抗氧化剂，在许多疾病模型中可保护神经元免受氧化应激。在此，我们研究了褪黑素对睡眠剥夺诱导的焦虑样行为的影响，并试图确定其中可能涉及的机制。采用改良多平台模型诱导大鼠发生睡眠剥夺。通过腹腔注射给予大鼠褪黑素（15毫克/千克）。采用高架十字迷宫试验、旷场试验和明暗箱试验评估焦虑样行为。测量血清皮质酮以确定应激水平。检测杏仁核和血清中的丙二醛（MDA）水平和超氧化物歧化酶（SOD）酶活性，以确定氧化应激水平。通过蛋白质印迹法检测蛋白质水平。结果表明，睡眠剥夺会诱发焦虑样行为，而褪黑素治疗可预防这些变化。血清皮质酮也随着睡眠剥夺而增加，但褪黑素使其水平恢复正常。此外，褪黑素逆转了睡眠剥夺诱导的杏仁核和血清中MDA和SOD的变化。蛋白质印迹结果表明，褪黑素减弱了睡眠剥夺大鼠中含NR2B的N-甲基-D-天冬氨酸受体、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体的GluR1亚基以及Ser831位点的GluR1磷酸化和钙/钙调蛋白依赖性蛋白激酶II-α的上调。同时，褪黑素阻止了γ-氨基丁酸A-α-2受体的下调。总之，我们的结果表明，褪黑素可预防睡眠剥夺诱导的焦虑样行为。可能的机制可能归因于其降低氧化应激以及维持γ-氨基丁酸能和谷氨酸能传递之间平衡的能力。
