Rapamycin relieves anxious emotion and synaptic plasticity deficits induced by hindlimb unloading in mice
Rapamycin relieves anxious emotion and synaptic plasticity deficits induced by hindlimb unloading in mice
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雷帕霉素缓解小鼠后肢卸载引起的焦虑情绪和突触可塑性缺陷
DOI：
10.1016/j.neulet.2018.04.033
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Tao Zhang
中科院分区：
文献类型：
--
作者：
Baohui Zhai;Xueliang Shang;Jingxuan Fu;Fangjuan Li;Tao Zhang
这项研究考察了增加自噬是否可以改善后肢卸载(HU)小鼠的认知障碍，该模型被用作突触可塑性损伤的动物模型。雄性C57BL/6小鼠随机分为3组：对照组、HU组和HU + 雷帕霉素组。采用后肢卸载法建立动物模型，持续2周。雷帕霉素以0.5 /kg/d的剂量在后肢卸载的同时予以注射。旷场试验和高架迷宫试验表明，雷帕霉素显著抑制了HU小鼠的焦虑水平和探索行为的增加。随后，记录在海马齿状回(DG)区的长时程增强(LTP)可被雷帕霉素有效地降低，而HU程序则明显抑制这一作用。此外，雷帕霉素进一步增加了自噬水平，而自噬水平在HU小鼠中已经升高。同时，雷帕霉素对HU小鼠N-甲基-D-天冬氨酸受体2A和2- B的表达有一定的调节作用。此外，雷帕霉素还能显著提高HU小鼠海马区总超氧化物歧化酶(T-SOD)活性，降低丙二醛(MDA)含量和碳化蛋白水平。结果表明，增加自噬可以安抚焦虑情绪，部分缓解海马区突触可塑性缺陷。
This study examined whether increasing autophagy could improve cognitive deficits in hindlimb unloaded (HU) mice, which was used as an animal model of synaptic plasticity impairment. Male C57BL/6 mice were randomly divided into three groups: control, HU and HU + rapamycin groups. Hindlimb unloading treatment was used to establish the animal model for 2 weeks. Rapamycin was intraperitoneally injected at a dose of 0.5 mg/kg/day along with hindlimb unloading procedure. The open field test and the elevated plus maze test showed that rapamycin considerably prevented the level of anxiety and increased exploratory behaviour in HU mice. Afterwards, long-term potentiation (LTP) recorded in the hippocampal dentate gyrus (DG) region was effectively reduced by rapamycin, which was significantly inhibited by HU procedure. In addition, rapamycin further increased the autophagy level, which was already elevated in HU mice. Meanwhile, the expression of NMDA receptor 2A and 2 B was modified by rapamycin in HU mice. Moreover, rapamycin noticeably increased the total superoxide dismutase (T-SOD) activity and reduced the malondialdehyde (MDA) as well as the level of carbonylated proteins in HU mice’s hippocampus. The results show that increasing autophagy may pacificate the anxious emotion, and partly alleviate the hippocampal synaptic plasticity deficits.
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影响因子：
--
作者：
Beckhauser TF;Francis-Oliveira J;De Pasquale R
通讯作者：
De Pasquale R
影响因子：
5.6
作者：
Wu X;Li D;Liu J;Diao L;Ling S;Li Y;Gao J;Fan Q;Sun W;Li Q;Zhao D;Zhong G;Cao D;Liu M;Wang J;Zhao S;Liu Y;Bai G;Shi H;Xu Z;Wang J;Xue C;Jin X;Yuan X;Li H;Liu C;Sun H;Li J;Li Y;Li Y
通讯作者：
Li Y
DOI：
10.1007/978-3-540-69361-1_2.2.6
发表时间：
2010-01-01
期刊：
VITILIGO
影响因子：
--
作者：
Picardo, Mauro;Dell'Anna, Maria Lucia
通讯作者：
Dell'Anna, Maria Lucia
DOI：
10.1016/j.jpba.2016.04.002
发表时间：
2016-06-05
影响因子：
3.4
作者：
Feng, Li;Yue, Xiao-fei;Chang, Qi
通讯作者：
Chang, Qi
影响因子：
3.4
作者：
Preiser, Jean-Charles
通讯作者：
Preiser, Jean-Charles