非侵入式静电场刺激对脂多糖诱导神经认知障碍小鼠的改善作用

魏国梁; 王聪; 孙书情; 刘贵松; 田学隆; 王星; 温惠中

doi:10.16016/j.2097-0927.202204192

您当前的位置：

首页 >

文章列表页 >

非侵入式静电场刺激对脂多糖诱导神经认知障碍小鼠的改善作用

神经科学 | 更新时间：2026-01-09

- 非侵入式静电场刺激对脂多糖诱导神经认知障碍小鼠的改善作用
- Improvement of noninvasive electrostatic field stimulation on lipopolysaccharide-induced neurocognitive impairment mice
- 陆军军医大学学报 2022年44卷第22期页码：2237-2245
- 作者机构：
  
  1.400044 重庆，重庆大学生物工程学院
  2.400038 重庆，陆军军医大学(第三军医大学)基础医学院神经生物学教研室，重庆市神经生物学重点实验室
- 作者简介：
  
  [王星，E-mail: wangxing@cqu.edu.cn WANG Xing, E-mail: wangxing@cqu.edu.cn
  [温惠中，E-mail: justzhong@sina.com WEN Huizhong, E-mail: justzhong@sina.com
- 基金信息：
  
  重庆市基础研究与前沿探索项目(cstc2018jcyjAX0506)
- DOI：10.16016/j.2097-0927.202204192
  中图分类号： R454.1;R741.05;R749.12
- 收稿：2022-04-26，
  
  修回：2022-07-07，
  
  纸质出版：2022-11-30
- 稿件说明：
移动端阅览
魏国梁, 王聪, 孙书情, 等. 非侵入式静电场刺激对脂多糖诱导神经认知障碍小鼠的改善作用[J]. 陆军军医大学学报, 2022,44(22):2237-2245.

Guoliang WEI, Cong WANG, Shuqing SUN, et al. Improvement of noninvasive electrostatic field stimulation on lipopolysaccharide-induced neurocognitive impairment mice[J]. Journal of Army Medical University, 2022, 44(22): 2237-2245.
魏国梁, 王聪, 孙书情, 等. 非侵入式静电场刺激对脂多糖诱导神经认知障碍小鼠的改善作用[J]. 陆军军医大学学报, 2022,44(22):2237-2245. DOI： 10.16016/j.2097-0927.202204192.

Guoliang WEI, Cong WANG, Shuqing SUN, et al. Improvement of noninvasive electrostatic field stimulation on lipopolysaccharide-induced neurocognitive impairment mice[J]. Journal of Army Medical University, 2022, 44(22): 2237-2245. DOI： 10.16016/j.2097-0927.202204192.

摘要

目的

探究非侵入式静电场刺激(noninvasive electrostatic field stimulation

NEFS)对脂多糖(lipopolysaccharide，LPS)诱导的神经认知障碍小鼠的改善作用。

方法

将48只3月龄雌性C57小鼠分为CTL组、NaCl+NEFS组、LPS+SHAM组、LPS+NEFS组，每组12只。LPS+NEFS组和LPS+SHAM组都以腹腔注射LPS(2 mg/kg)的方式建立神经认知障碍模型，建模后，连续进行4 d的NEFS治疗，其中LPS+NEFS组接受160 kV/m的静电场刺激(30 min/d)而LPS+SHAM组只接受0 kV/m的假刺激(3 s/d)。NaCl+NEFS组注射等量0.9%生理盐水代替LPS并进行160 kV/m的静电场刺激；CTL组不做任何处理。NEFS后，用T迷宫(T-maze)实验和新物体识别(new object recognition

NOR)实验观察小鼠的认知能力；用免疫组化技术检测小鼠海马神经元的数量；用免疫荧光技术检测小鼠海马星形胶质细胞的变化。

结果

与CTL组比较，LPS+SHAM组在T-maze和NOR中的学习记忆能力显著减弱(

0.05)，且海马区神经元的数目显著减少而活化的星形胶质细胞的数目显著增加(

0.05)。而与LPS+SHAM组比较，LPS+NEFS组在T-maze和NOR中的学习记忆能力显著提高(

0.05)，且海马区神经元的数目也显著增加(

0.05)，星形胶质细胞的增生被显著抑制(

0.05)。

结论

腹腔注射2 mg/kg的LPS可以建立神经认知障碍模型，NEFS对LPS诱导神经认知障碍小鼠起到改善作用。

Abstract

Objective

To explore the improvement of noninvasive electrostatic field stimulation (NEFS) on neurocognitive impairment mice induced by lipopolysaccharide (LPS).

Methods

Forty-eight female C57 mice aged 3 months were divided into the CTL group

the NaCl+NEFS group

the LPS+SHAM group and the LPS+NEFS group

with 12 mice in each group. Both the LPS+NEFS group and the LPS+SHAM group were injected with 2 mg/kg LPS intraperitoneally to establish the mouse model of neurocognitive impairment

and after the model was constructed

they were treated with NEFS for 4 d

during which the LPS+NEFS group received an electrostatic field of 160 kV/m for 30 min/d while the LPS+SHAM group were only stimulated by an electrostatic field of 0 kV/m for 3 s/d. The NaCl+NEFS group was injected with the same amount of 0.9% normal saline instead of LPS and stimulated by electrostatic field (160 kV/m); The CTL group was a no-treatment group. After NEFS

the cognitive ability of mice was observed by T maze experiment (T-maze) and the new object recognition (NOR) experiment. Immunohistochemical method was used to detect the number of hippocampal neurons in mice

and immunofluorescence method was used to detect the changes of hippocampal astrocytes.

Results

Compared with the results of behavioral experiment and morphological observation of the CTL group

the learning and memory abilities of the LPS+SHAM group in T-maze and NOR was significantly weakened (

0.05)

and the number of neurons in hippocampus decreased significantly while the number of activated astrocytes increased significantly (

0.05). Furthermore

compared with the LPS+SHAM group

the learning and memory abilities of the LPS+NEFS group in T-maze and NOR was significantly improved (

0.05)

and the number of neurons in hippocampus was also significantly increased (

0.05)

and the proliferation of astrocytes was significantly inhibited (

0.05).

Conclusion

Intraperitoneal injection of 2 mg/kg LPS can establish neurocognitive impairment model

and NEFS has protective effect on LPS-induced neurocognitive impairment in mice.

关键词

Keywords

references

KWON H S, KOH S H. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes[J]. Transl Neurodegener, 2020, 9(1): 42. DOI: 10.1186/s40035-020-00221-2.

CHOI S H, BYLYKBASHI E, CHATILA Z K, et al . Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model[J ] . Science, 2018, 361(6406). DOI: 10.1126/science.aan8821.

LIDDELOW S A, GUTTENPLAN K A, CLARKE L E, et al . Neurotoxic reactive astrocytes are induced by activated microglia[J ] . Nature, 2017, 541(7638): 481-487. DOI: 10.1038/nature21029.

BATISTA C R A, GOMES G F, CANDELARIO-JALIL E, et al . Lipopolysaccharide-induced neuroinflammation as a bridge to underst and neurodegeneration[J ] . Int J Mol Sci, 2019, 20(9). DOI: 10.3390/ijms20092293.

张翔南. LPS腹腔注射诱发大鼠脑内炎症致皮层与海马病理改变及相关机制研究[D]. 浙江大学, 2010.

ZHANG X N. Pathological changes and related mechanisms in rat cortex and hippocampus after intraperitoneal injection of LPS-induced brain inflammation[D]. Hangzhou: Zhejiang University, 2010.

BROWN G C. The endotoxin hypothesis of neurodegeneration[J]. J Neuroinflammation, 2019, 16(1): 180. DOI: 10.1186/s12974-019-1564-7.

张艺瀚, 葛立军, 徐申瑶, 等. 腹腔注射脂多糖致大鼠炎症模型海马区损伤表征[C]. 中国毒理学会第七次全国毒理学大会暨第八届湖北科技论坛论文集. 2015.

ZHANG Y H, GE L J, XU S Y, et al . Characterization of hippocampal damage induced by intraperitoneal injection of lipopoly saccharide in an inflammatory rat model[C ] . The 7th National Congress of Toxicology, Chinese Society of Toxic ology (CSOT-VⅡ) and the 8th Hubei Science and Technology Forum. 2015.

GROSSMAN N, BONO D, DEDIC N, et al . Noninvasive deep brain stimulation via temporally interfering electric fields[J ] . Cell, 2017, 169(6): 1029-1041. DOI: 10.1016/j.cell.2017.05.024..

BERZHANSKAYA J, CHERNYY N, GLUCKMAN B J, et al . Modulation of hippocampal rhythms by subthreshold electric fields and network topology[J ] . J Comput Neurosci, 2013, 34(3): 369-389. DOI: 10.1007/s10827-012-0426-4.

梁媛媛, 涂晔, 安晓强, 等. 静电场调控p53合成对成纤维细胞增殖周期的影响[J]. 解剖学杂志, 2021, 44(02): 114-117+135. DOI: 10.3969/j.issn.1001-1633.2021.02.005.

LIANG Y Y, TU Y, AN X Q, et al . Effect of regulating p53 synthesis by electrostatic field on proliferation cycle of fibroblast[J ] . Chin J Anat, 2021, 44(02): 114-117+135. DOI: 10.3969/j.issn.1001-1633.2021.02.005.

于凯, 王江, 邓斌, 等. 外电场作用下神经元网络同步特性[J]. 计算机应用研究, 2014, 31(1): 70-75. DOI: 10.3969/j.issn.1001-3695.2014.01.016.

YU K, WANG J, DENG B, et al . Synchronization characteristics of neural network subject to external electric field[J ] . App Res of Comput, 2014, 31(1): 70-75. DOI: 10.3969/j.issn.1001-3695.2014.01.016.

DENG Z D, LISANBY S H, PETERCHEV A V. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study[J]. J Neural Eng, 2011, 8(1): 016007. DOI: 10.1088/1741-2560/8/1/016007.

王连坤. 高功率脉冲微波辐照大鼠体内电场分布的数值模拟和实验验证[D]. 华东师范大学, 2010.

WANG L K. The numerical simulation and experimental verifi cation of electric field distribution in rat by high power pulse microwave irradiation[D]. Shanghai: East China Normal University, 2010.

CARRATALA-ROS C, OLIVARES-GARCIA R, MARTINEZ-VERDU A, et al . Energizing effects of bupropion on effortful behaviors in mice under positive and negative test conditions: modulation of DARPP-32 phosphorylation patterns[J ] . Psychopharmacology (Berl), 2021, 238(12): 3357-3373. DOI: 10.1007/S00213-021-05950-4.

ZHANG R, XUE G, WANG S, et al . Novel object recognition as a facile behavior test for evaluating drug effects in A beta PP/PS1 Alzheimer's disease mouse model[J ] . J Alzheimers Dis, 2012, 31(4): 801-812. DOI: 10.3233/JAD-2012-120151.

XIN Y R, JIANG J X, HU Y, et al . The immune system drives synapse loss during lipopolysaccharide-induced learning and memory impairment in mice[J ] . Front Aging Neurosci, 2019, 11: 279. DOI: 10.3389/fnagi.2019.00279.

LEE J, LEE Y, YUK D, et al . Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation[J ] . J Neuroinflamm, 2008, 5: 37. DOI: 10.1186/1742-2094-5-37.

SHARIATIRAD S, VAZIRI A, HASSANI-ABHARIAN P, et al . Cumulative and booster effects of tDCS sessions on drug cravings, lapse, and cognitive impairment in methamphetamine use disorder: A case study report[J ] . Am J Addict, 2016, 25(4): 264-266. DOI: 10.111/ajod-12373.

NIEH E H, SCHOTTDORF M, FREEMAN N W, et al . Geometry of abstract learned knowledge in the hippocampus[J ] . Nature, 2021, 595(7865): 80-84. DOI: 10.1038/S41586-021-03652-7.

GIGUERE N, NANNI S B, TRUDEAU L E. On cell loss and selective vulnerability of neuronal populations in Parkinson's disease[J]. Front Neurol, 2018, 9: 455. DOI: 10.3389/fneur.2018.00455.

GONZALEZ-REYES R E, NAVA-MESA M O, VARGAS-SANCHEZ K, et al . Involvement of astrocytes in Alzheimer's disease from a neuroinflammatory and oxidative stress perspective[J ] . Front Mol Neurosci, 2017, 10: 427. DOI: 10.3389/fnmol.2017.00427.

RODRIGUEZ-ARELLANO JJ, PARPURA V, ZOREC R, et al . Astrocytes in physiological aging and Alzheimer's disease[J ] . Neuroscience, 2016, 323: 170-182. DOI: 10.1016/j.neuroscience.2015.01.007.

ESTRADA C, FERNANDEZ-GOMEZ F J, LOPEZ D, et al . Transcranial magnetic stimulation and aging: effects on spatial learning and memory after sleep deprivation in Octodon degus[J ] . Neurobiol Learn Mem, 2015, 125: 274-281. DOI: 10.1016/j.nlm.2015.09.011.

ZHANG K Y, RUI G, ZHANG J P, et al . Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke[J ] . BMC Neurosci, 2020, 21(1): 21. DOI: 10.1186/s12868-020-00570-8.

孟凡刚, 张建国. 自适应脑深部电刺激术治疗运动障碍性疾病研究进展[J]. 中国现代神经疾病杂志, 2022, 22(04): 217-223. DOI: 10.3969/j.issn.1672-6731.2022.04.001.

MENG F G, ZHANG J G. Adaptive deep brain stimulation for motor disorders[J]. Chin J Contemp Neurol Neurosurg, 2022, 22(04): 217-223. DOI: 10.3969/j.issn.1672-6731.2022.04.001.

KANTAR G D, AKPINAR D, YARGICOGLU P, et al . Effects of extremely low-frequency electric fields at different intensities and exposure durations on mismatch negativity[J ] . Neuroscience, 2014, 272: 154-166. DOI: 10.1016/j.neuroscience.2014.04.056.

DI G Q, KIM H, XU Y Q, et al . A comparative study on influences of static electric f ield and power frequency electric field on cognition in mice[J ] . Environ Toxicol Pharmacol, 2019, 66: 91-95. DOI: 10.1016/j.etap.2019.01.001.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

柚皮苷改善脂多糖诱导的小鼠抑郁样行为的作用研究

嗜铬粒蛋白A衍生多肽CHR抑制LPS诱导的永生化脑微血管内皮细胞高通透性

胞外DNA在急性呼吸窘迫综合征小鼠炎症损伤中的作用

大胞饮途径介导血管平滑肌细胞内脂滴聚集

双氢青蒿素抑制LPS诱导的小胶质细胞炎症反应