当前位置: X-MOL 学术Neurochem. Int. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Nicotine alleviates chronic stress-induced anxiety and depressive-like behavior and hippocampal neuropathology via regulating autophagy signaling
Neurochemistry international ( IF 4.2 ) Pub Date : 2018-01-16
Xi Xiao, Xueliang Shang, Baohui Zhai, Hui Zhang, Tao Zhang

Recently, we reported that chronic nicotine significantly improved chronic stress-induced impairments of cognition and the hippocampal synaptic plasticity in mice, however, the underlying mechanism still needs to be explored. In the present study, 32 male C57BL/6 mice were divided into four groups: control (CON), stress (CUS), stress with chronic nicotine administration (CUS + Nic) and chronic nicotine administration (Nic). The anxiety-like behavior and neuropathological alteration of DG neurons were examined. Moreover, PC12 cells were examined with corticosterone in the presence or absence of nicotine. Both cell viability and apoptosis were determined. When treated simultaneously with an unpredictable chronic mild stress (CUS), nicotine (0.2 mg/kg/d) attenuated behavioral deficits and neuropathological alterations of DG neurons. Moreover, Western blotting showed that chronic nicotine also elevated the level of autophagy makers including Beclin-1 and LC3 II triggered by CUS. In addition, concomitant treatment with nicotine (10 μM) significantly attenuated the loss of PC12 cell viability (p < .01) and apoptosis compared to that of corticosterone treatment alone. Besides, chronic nicotine also enhanced the protein and RNA expression levels of autophagy makers triggered by corticosterone, such as Beclin-1, LC3 II and p62/SQSTM1. However, the above improvements were significantly blocked by autophagy inhibitor 3-MA. Importantly, the activation of the PI3K/Akt/mTOR signaling was carefully tested to illuminate the effects of chronic nicotine. Consequently, chronic nicotine played a role of neuroprotection in either CUS mice or corticosterone cells associating with the enhancement of the autophagy signaling, which was involved in activating the PI3K/Akt/mTOR signaling.



中文翻译:

尼古丁通过调节自噬信号减轻慢性应激引起的焦虑和抑郁样行为以及海马神经病理学

最近,我们报道了慢性尼古丁可显着改善小鼠慢性应激诱导的认知障碍和海马突触可塑性,但是,其潜在机制仍需探索。在本研究中,将32只雄性C57BL / 6小鼠分为四组:对照组(CON),应激(CUS),慢性尼古丁给药(CUS + Nic)和慢性尼古丁给药(Nic)。检查了DG神经元的焦虑样行为和神经病理改变。此外,在存在或不存在尼古丁的情况下,用皮质酮检查PC12细胞。测定细胞活力和凋亡。当与不可预测的慢性轻度应激(CUS)同时治疗时,尼古丁(0.2 mg / kg / d)可减轻DG神经元的行为缺陷和神经病理改变。而且,蛋白质印迹表明,慢性尼古丁还升高了由CUS触发的自噬分子(包括Beclin-1和LC3 II)的水平。此外,相较于单独使用皮质酮治疗,尼古丁(10μM)的伴随治疗显着减轻了PC12细胞活力的丧失(p <.01)和细胞凋亡。此外,慢性尼古丁还增强了由皮质酮触发的自噬基因的蛋白质和RNA表达水平,例如Beclin-1,LC3 II和p62 / SQSTM1。但是,自噬抑制剂3-MA明显阻碍了上述改善。重要的是,对PI3K / Akt / mTOR信号的激活进行了仔细的测试,以阐明慢性尼古丁的作用。所以,

更新日期:2018-01-17
down
wechat
bug