Chronic N-acetylcysteine treatment alleviates acute lipopolysaccharide-induced working memory deficit through upregulating caveolin-1 and synaptophysin in mice
Chronic N-acetylcysteine treatment alleviates acute lipopolysaccharide-induced working memory deficit through upregulating caveolin-1 and synaptophysin in mice
复制标题
慢性 N-乙酰半胱氨酸治疗可通过上调小鼠的 Caveolin-1 和突触素来缓解急性脂多糖诱导的工作记忆缺陷。
DOI：
10.1007/s00213-017-4762-y
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发表时间：
2018
影响因子：
3.4
通讯作者：
Jin Xinchun
中科院分区：
文献类型：
--
作者：
Shen Xianzhi;Sun Yanyun;Wang Mengwei;Shu Hui;Zhu Li Juan;Yan Pei Yun;Zhang Jun Fang;Jin Xinchun
工作记忆是一个动态的编码过程，是信息在短时间内的主动表征。如果WM受到各种因素的损害，包括炎症，压力，自由基和疾病状态，如精神分裂症，那么指导未来行为的能力就会被破坏。然而，急性工作记忆损害的机制仍有待defined.ObjectivesIn这项研究中，我们测试的假设，减少小窝蛋白-1（Cav-1）和突触素（SYP）占WM损害挑战急性腹腔内脂多糖（LPS），模仿神经炎症。采用延迟交替T迷宫（DAT）测试成年雄性C57 BL/6小鼠的工作记忆，采用免疫印迹和免疫组化方法检测内侧前额叶皮层（mPFC）和海马中Cav-1和SYP蛋白的表达和分布。此外，LPS通过激活小胶质细胞，显著降低神经元中Cav-1和SYP的蛋白水平。更重要的是，2周的N-乙酰半胱氨酸（NAC）治疗剂量依赖性地抑制LPS诱导的工作记忆缺陷的能力，提高使用Lose-shift，但不Win-shift策略，并显着抑制LPS诱导下调的Cav-1和SYP在mPFC.ConclusionsTaken，我们的研究结果表明，慢性NAC治疗加重急性LPS诱导的工作记忆缺陷，通过上调Cav-1和SYP在小鼠。
RationaleWorking memory (WM) is a dynamic encoding process and an active representation of information over a short time. The ability to guide forthcoming behavior would be disrupted if WM was impaired by various factors including inflammation, stress, free radicals, and disease states such as schizophrenia. However, the mechanism underlying acute working memory impairment remains to be defined.ObjectivesIn this study, we tested the hypothesis that decreased caveolin-1 (Cav-1) and synaptophysin (SYP) accounted for the WM impairment challenged with acute intraperitoneally lipopolysaccharide (LPS), which mimicked neuroinflammation. Delayed alternation T-maze task (DAT) was used to assess working memory of adult male C57BL/6 mice, and western blot and immunostaining were used to detect protein expression and distribution in medial prefrontal cortex (mPFC) and hippocampus.ResultsOur results showed that LPS dose-dependently induced working memory deficit accompanied by the decrease of Cav-1 and SYP in mPFC but not hippocampus. In addition, LPS significantly decreased protein level of Cav-1 and SYP in neurons by activating microglia cells. More important, 2-week N-acetylcysteine (NAC) treatment dose-dependently inhibited LPS-induced working memory deficit by improving the ability to use Lose-shift but not Win-shift strategy and significantly inhibited LPS-induced downregulation of Cav-1 and SYP in mPFC.ConclusionsTaken together, our findings demonstrate that chronic NAC treatment alleviates acute LPS-induced working memory deficit through upregulating Cav-1 and SYP in mice.