Vitamin C and vitamin E double-deficiency increased neuroinflammation and impaired conditioned fear memory
Vitamin C and vitamin E double-deficiency increased neuroinflammation and impaired conditioned fear memory
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维生素C和维生素E双重缺乏会增加神经炎症并损害条件性恐惧记忆
DOI：
10.1016/j.abb.2019.01.003
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发表时间：
2019
影响因子：
3.9
通讯作者：
Ishigami Akihito
中科院分区：
文献类型：
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作者：
Takahashi Keita;Yanai Shuichi;Takisawa Shoko;Kono Nozomu;Arai Hiroyuki;Nishida Yoichiro;Yokota Takanori;Endo Shogo;Ishigami Akihito
维生素C （l-抗坏血酸，VC）和维生素E （α-生育酚，VE）作为内源性抗氧化剂在许多组织和器官中发挥着重要的生理作用。然而，它们在大脑中的作用仍然完全难以捉摸。我们建立衰老标志蛋白30 (SMP30)/α-生育酚转移蛋白（αTTP）双敲除（DKO）小鼠作为VC和VE双缺乏的新模型，观察VC和VE双缺乏对脑功能的影响。方法将sdko和野生型（WT）小鼠分为两组：CE（+）组给予足量的VC和VE， CE（−）组同时缺乏VC和VE。在8周的CE（+）或CE（−）治疗后，通过Morris水迷宫和巴甫洛夫恐惧条件反射任务进行一系列行为实验来分析认知功能，包括记忆。结果DKO-CE（−）小鼠血浆VC、VE水平和WT-CE（−）小鼠血浆VE水平在8周后几乎完全缺失。行为学研究显示，CE（−）处理对DKO和WT小鼠的一般行为（包括运动活动和焦虑水平）没有影响。然而，在巴甫洛夫恐惧条件反射任务中，与DKO-CE（+）小鼠相比，DKO-CE（−）小鼠表现出条件恐惧记忆受损。此外，DKO-CE（−）小鼠海马中炎症相关基因IL-6、TNFα、F4/80和Mcp-1的mRNA表达增加。结论VC和VE缺乏导致条件性恐惧记忆受损，可能与脑内神经炎症有关。
BackgroundVitamin C (l-ascorbic acid, VC) and vitamin E (α-tocopherol, VE) play important physiological roles as endogenous antioxidants in many tissues and organs. However, their roles in the brain remain entirely elusive. We established senescence marker protein 30 (SMP30)/α-tocopherol transfer protein (αTTP) double knockout (DKO) mice as a novel VC and VE double-deficiency model and examined the effect of VC and VE double-deficiency on brain functions.MethodsDKO and wild-type (WT) mice were divided into the following two groups: mice in the CE (+) group were supplied with sufficient amounts of VC and VE and mice in the CE (−) group were deficient in both VC and VE. After 8 weeks of CE (+) or CE (−) treatments, a battery of behavioral experiments was conducted to analyze cognitive functions, including memory, through the Morris water maze and Pavlovian fear conditioning tasks.ResultsThe plasma VC and VE levels in DKO-CE (−) mice and VE level in WT-CE (−) mice were almost completely depleted after 8 weeks of the deficient treatment. The behavioral study revealed that the general behaviors, including locomotor activity and anxiety level, were not influenced by the CE (−) treatment in DKO and WT mice. However, in the Pavlovian fear conditioning task, DKO-CE (−) mice showed impaired conditioned fear memory compared with that of DKO-CE (+) mice. Furthermore, increased mRNA expression was observed in inflammatory-related genes, such as IL-6, TNFα, F4/80, and Mcp-1, in the hippocampus of DKO-CE (−) mice.ConclusionsThe findings of this study provide evidence that VC and VE deficiency led to impaired conditioned fear memory possibly caused by neuroinflammation in the brain.