中国医科大学学报

中国医科大学学报
  • 中文核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
  • BA、CA收录

中国医科大学学报 ›› 2018, Vol. 47 ›› Issue (3): 217-221.doi: 10.12007/j.issn.0258-4646.2018.03.006

• 论著 • 上一篇    下一篇

β-淀粉样蛋白诱导的阿尔茨海默病大鼠模型中BDNF与TRPC3的关系

张利华, 张丽艳, 张小康, 徐超龙, 周义   

  1. 沈阳医学院基础医学院病理生理学教研室, 沈阳 110034
  • 收稿日期:2017-10-30 出版日期:2018-03-30 发布日期:2018-03-24
  • 通讯作者: 张丽艳 E-mail:1580471013@qq.com
  • 作者简介:张利华(1990-),女,硕士研究生.
  • 基金资助:
    辽宁省自然科学基金(20170540874);沈阳医学院科学研究基金(20171008);辽宁省大学生创新创业训练计划(201610164002)

Relationship between BDNF and TRPC3 in a Rat Model of Alzheimer's Disease Induced by β-amyloid Protein

ZHANG Lihua, ZHANG Liyan, ZHANG Xiaokang, XU Chaolong, ZHOU Yi   

  1. Department of Pathophysiology, College of Basic Medical Sciences, Shenyang Medical College, Shenyang 110034, China
  • Received:2017-10-30 Online:2018-03-30 Published:2018-03-24

摘要: 目的 探讨经典瞬时受体电位通道蛋白3(TRPC3)与脑源性神经营养因子(BDNF)在阿尔茨海默病(AD)大鼠模型海马组织中的表达及其相互关系。方法 将SD大鼠随机分为PBS组、AD组和AD+BDNF组。采用β-淀粉样蛋白(Aβ1-42)侧脑室注射,制备AD模型。BDNF在造模14 d后经侧脑室导管注入。Morris水迷宫实验测定大鼠的空间学习记忆能力。实时PCR和Western blotting分别检测海马组织中TRPC3BDNF mRNA和蛋白的表达情况。结果 Morris水迷宫实验表明,AD组大鼠第5天逃避潜伏期较PBS组延长(P < 0.05);AD+BDNF组大鼠的逃避潜伏期较AD组缩短(P < 0.05)。实时PCR及Western blotting结果表明,与PBS组相比,TRPC3BDNF mRNA和蛋白在AD组表达均降低(P < 0.05);与AD组相比,TRPC3 mRNA和蛋白在AD+BDNF组表达均增高(P < 0.05)。结论 BDNF和TRPC3在AD大鼠海马组织表达降低;外源性BDNF可能通过上调TRPC3表达,从而改善Aβ1-42导致的AD大鼠空间学习记忆障碍,起到保护神经元的作用。

关键词: 经典瞬时受体电位通道蛋白3, 阿尔茨海默病, β-淀粉样蛋白, 脑源性神经营养因子

Abstract: Objective To investigate the expression and relationship of canonical transient receptor potential channel-3 (TRPC3) and brain-derived neurotrophic factor (BDNF) in the hippocampus of a rat model of Alzheimer's disease (AD). Methods SD rats were randomly divided into PBS,AD,and AD+BDNF experimental groups. AD models were generated by intracerebroventricular injection of β-amyloid protein (Aβ1-42). BDNF was injected via the lateral ventricle catheter after 14 days. The Morris water maze test was used to assess the spatial learning and memory ability of the rats. The expression of TRPC3 and BDNF mRNA and protein in the hippocampus were detected by RT-PCR and Western blotting,respectively. Results The Morris water maze test showed that the escape latencies of the fifth day in the AD group were longer than those in the PBS group (P < 0.05). The escape latencies in the AD+BDNF group were shorter than those in the AD group (P < 0.05). RT-PCR and Western blotting results showed that the expression of both TRPC3 and BDNF were reduced in the AD group compared with the PBS group (P < 0.05). TRPC3 expression was increased in the AD+BDNF group compared with the AD group (P < 0.05). Conclusion The expression of BDNF and TRPC3 is decreased in the hippocampus of AD rats. An exogenous BDNF injection appears to improve the spatial learning and memory of AD rats that are impaired by a Aβ1-42 injection,possibly via TRPC3 upregulation,and may play a protective role in neurons.

Key words: canonical transient receptor potential channel-3, Alzheimer's disease, β-amyloid protein, brain-derived neurotrophic factor

中图分类号: 

  • R749.16
[1] DINIZ BS,TEIXEIRA AL. Brain-derived neurotrophic factor and Alzheimer's disease:physiopathology and beyond[J]. Neuromolecular Med,2011,13(4):217-222. DOI:10.1007/s12017-011-8154-x.
[2] AMARAL M D,POZZOMILLER L. TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a nonselective cationic current and to induce dendritic spine formation[J]. Neurosci,2007,27(19):5179-5189. DOI:10.1523/JNEUROSCI.5499-06.2007.
[3] CHAO G,MA Y,MA S,et al. The role of TRPC6 in the neuroprotection of calycosin against cerebral ischemic injury[J]. Sci Rep,2017,7(1):3039. DOI:10.1038/s41598-017-03404-6.
[4] YANG ZW,WU F,ZHANG SL. Effects of ganoderic acids on epileptiform discharge hippocampal neurons:insights from alterations of BDNF,TRPC3 and apoptosis[J]. Pharmazie,2016,71(6):340-344. DOI:10.1691/ph.2016.5889.
[5] 张改改,张丽艳,邹丹,等. 经典瞬时受体电位通道蛋白在β淀粉样蛋白诱导的阿尔茨海默病小鼠海马区的表达[J]. 中国医科大学学报,2016,45(12):1100-1104. DOI:10.12007/j.issn.0258-4646. 2016.12.010.
[6] 于方,拓西平,吕建勇. 侧脑室注射β-淀粉样蛋白制作阿尔茨海默病样大鼠模型[J]. 实用老年医学,2010,24(6):475-478. DOI:10. 3969/j.issn.1003-9198.2010.06.011.
[7] WEI Z,CHEN XC,SONG Y,ET AL. Amyloid β protein aggravates neuronal senescence and cognitive deficits in 5XFAD mouse model of Alzheimer's disease[J]. Chin Med J (Engl),2016,129(15):1835-1844. DOI:10.4103/0366-6999.186646.
[8] NAGAHARA AH,MATELING M,KOVACS I,et al. Early BDNF treatment ameliorates cell loss in the entorhinal cortex of APP transgenic mice[J]. Neurosci,2013,33(39):15596-15602. DOI:10.1523/JNEUROSCI.5195-12.2013.
[9] ZHANG L,FANG Y,LIAN Y,et al. Brain-derived neurotrophic factor ameliorates learning deficits in a rat model of Alzheimer's disease induced by Aβ1-42[J]. PLoS One,2015,10(4):e0122415. DOI:10. 1371/journal.pone.0122415.
[10] HANG P,ZHAO J,CAI B,ET al. Brain-derived neurotrophic factor regulates TRPC3/6 channels and protects against myocardial infarction in rodents[J]. Int J Biol Sci,2015,11(5):536-545. DOI:10.7150/ijbs.10754.
[11] FORTIN DA,SRIVASTAVA T,DWARAKANATH D,et al. BDNF activation of CaM-kinase kinase via TRPC channels induces the translation and synaptic incorporation of GluA1 containing calcium-permeable AMPARs[J]. Neurosci,2012,32(24):8127-8137. DOI:10.1523/JNEUROSCI.6034-11.2012.
[12] SAWAMURA S,HATANO M,TAKADA Y,et al. Screening of transient receptor potential canonical channel activators identifies novel neurotrophic piperazine compounds[J]. Mol Pharmacol,2016,89(3):348-363. DOI:10.1124/mol.115.102863.
[1] 王海英, 李慧源, 罗红月, 张慧予, 姜扬, 郭利晴, 陶蕾, 孙晓红. 青蒿素调控NF-κB信号通路介导阿尔茨海默病炎症反应细胞模型的研究[J]. 中国医科大学学报, 2018, 47(6): 552-555,561.
[2] 王思亓, 李欣潞, 林庚, 王卓, 程晓凤, 刘彤彤, 郑玮. DMT1在APP/PS1转基因小鼠小脑皮质中表达上调[J]. 中国医科大学学报, 2018, 47(3): 193-197.
[3] 张改改,张丽艳,邹丹,沈薇,金戈,张利华. 经典瞬时受体电位通道蛋白在 β 淀粉样蛋白诱导的阿尔茨海默病 小鼠海马区的表达[J]. 中国医科大学学报, 2016, 45(12): 1100-1104.
[4] 丛琳,张楠楠,佡剑非,任艳. 甲基化芯片检测APP/PS1双转基因小鼠基因组DNA甲基化分布[J]. 中国医科大学学报, 2015, 44(2): 160-163.
[5] 费洪新,韩玉生,杜徽,姜波,李宝龙,朴成玉,张英博,仲丽丽,白云,周忠光. 补阳还五汤对APP/PS1双转基因小鼠学习记忆及海马组织白介素?6水平的影响[J]. 中国医科大学学报, 2014, 43(8): 677-681.
[6] 闫荣,张尧,罗晓光,李宇凤,冯娟. 星形胶质细胞条件培养液诱导骨髓基质细胞向神经元样细胞分化的神经营养机制探讨[J]. 中国医科大学学报, 2013, 42(8): 714-721.
[7] 徐爱华,孙永新,商秀丽. 外源性脑源性神经营养因子通过抑制tau蛋白磷酸化减少细胞凋亡[J]. 中国医科大学学报, 2013, 42(4): 296-300.
[8] 闫荣,罗晓光,张尧,李宇凤冯娟. 星形胶质细胞影响神经干细胞突触表达的神经营养家族基因表达机制探讨[J]. 中国医科大学学报, 2013, 42(11): 989-995.
[9] 赵彬,商秀丽 ,何志义,范国光,刘虎. 阿尔茨海默病的静息态fMRI低频振幅研究[J]. 中国医科大学学报, 2012, 41(4): 329-332.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!

中国医科大学学报版权所有©2018

未经允许,严禁擅自转载本站图文资料

地址:中国 沈阳市沈北新区蒲河路77号 110122

辽ICP备05014850

JOURNAL OF CHINA MEDICAL UNIVERSITY

ADDRESS: NO.77 PUHE ROAD

SHENYANG NORTH NEW AREA, SHENYANG

LIAONING PROVINCE, P.R. CHINA