MPTP诱导野生型和A53T转基因型小鼠帕金森病模型纹状体中神经递质变化

doi:10.19803/j.1672-8629.2021.04.04

中国药物警戒 ›› 2021, Vol. 18 ›› Issue (4): 315-319.
DOI: 10.19803/j.1672-8629.2021.04.04

• 帕金森病药物研究模型专栏 • 上一篇下一篇

MPTP诱导野生型和A53T转基因型小鼠帕金森病模型纹状体中神经递质变化

王硕, 温路, 张程璐, 王茹璇, 陈乃宏, 苑玉和^*

中国医学科学院药物研究所,北京 100050

收稿日期:2020-12-31 出版日期:2021-04-15 发布日期:2021-04-23
通讯作者: ^*苑玉和,女,博士,研究员·博导,神经退行性疾病。E-mail：yuanyuhe@imm.ac.cn
作者简介:王硕,男,博士,神经药理学。
基金资助:
国家自然科学基金项目（81773925）

Changes of Neurotransmitters in the Striatum of MPTP-induced Wild-type and A53T Transgenic Mouse Parkinson's Disease Models

WANG Shuo, WEN Lu, ZHANG Chenglu, WANG Ruxuan, CHEN Naihong, YUAN Yuhe^*

Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Received:2020-12-31 Online:2021-04-15 Published:2021-04-23

摘要/Abstract

摘要： 目的探究帕金森病（Parkinson’s disease, PD）小鼠模型纹状体中多巴胺等神经递质的变化。方法通过腹腔注射丙磺舒（probenecid）、皮下注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP）制备PD野生型小鼠和A53T转基因小鼠急性模型和野生型小鼠慢性模型;通过高效液相色谱法（high-performance liquid chromatography, HPLC）检测小鼠纹状体中神经递质的变化。结果 HPLC结果显示,MPTP可以诱导野生型和A53T转基因小鼠纹状体中多巴胺（dopamine, DA）递质水平降低,二羟基苯乙酸（dihydroxyphenylacetic acid, DOPAC）水平降低,高香草酸（homovanillic acid, HVA）的水平降低,二羟基苯乙醛（dihydroxy phenylacetaldehyde, DOPAL）的含量升高,而对5-羟色胺（serotonin, 5-HT）和去甲肾上腺素（norepinephrine, NE）无显著影响。结论 MPTP诱导能够导致DA递质水平降低,以及其毒性代谢产物DOPAL含量增加,从而会促进PD的发生发展。

关键词: 帕金森病, 1-甲基-4-苯基-1,2,3,6-四氢吡啶, 纹状体, A53T, 神经递质

Abstract: Objective To explore the changes of such neurotransmitters as dopamine in the striatum of mouse models with Parkinson's disease (PD). Methods An acute PD model of A53T transgenic mice and a chronic PD model of wild-type mice were induced via intraperitoneal injection of probenecid and subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). High-performance liquid chromatography (HPLC) was used to detect the changes of neurotransmitters in the mouse striatum. Results HPLC results showed that MPTP could induce an decrease of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) in the striatum, and an increase of dihydroxy phenylacetaldehyde (DOPAL). But the contents of serotonin (5-HT) and norepinephrine (NE) did not change significantly. Conclusion MPTP can induce a decrease in the level of DA transmitters and an increase in the content of its toxic metabolite DOPAL, thereby promoting the occurrence and development of PD.

Key words: Parkinson's disease, MPTP, striatum, A53T, neurotransmitter

中图分类号:

R994.1

王硕, 温路, 张程璐, 王茹璇, 陈乃宏, 苑玉和. MPTP诱导野生型和A53T转基因型小鼠帕金森病模型纹状体中神经递质变化[J]. 中国药物警戒, 2021, 18(4): 315-319.

WANG Shuo, WEN Lu, ZHANG Chenglu, WANG Ruxuan, CHEN Naihong, YUAN Yuhe. Changes of Neurotransmitters in the Striatum of MPTP-induced Wild-type and A53T Transgenic Mouse Parkinson's Disease Models[J]. Chinese Journal of Pharmacovigilance, 2021, 18(4): 315-319.

参考文献

[1] Teri Capriotti.Parkinson disease[J]. Home Healthcare Now, 2016, 34(6): 300-307.
[2] Alves G, Forsaa EB, Pedersen KF, et al.epidemiology of parkinson's disease[J]. J Neural Transm (Vienna), 2017, 124(8): 901-905.
[3] Abeliovich A, Rhinn H.Parkinson's disease: guilt by genetic association[J]. Nature, 2016, 533(7601): 40-41.
[4] Henrich MT, Geibl FF, Lee B, et al.A53T-α-synuclein overexpression in murine locus coeruleus induces Parkinson's disease-like pathology in neurons and glia[J]. Acta Neuropathol Commun, 2018, 6(1): 39.
[5] Zhou TT, Zhang QS.Effects of bibenzyl compound (20C) from gastrodia elata on MPTP/p-induced mice and mechanism[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2020, 17(11): 753-757,772.
[6] Zhang QS, Chen Y.Parkinsonian lesion in rat induced by rotenone and its possible mechanism[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2017, 14(9): 513-517.
[7] Mattammal MB, Haring JH, Chung HD, et al.An endogenous dopaminergic neurotoxin: implication for Parkinson's disease[J]. Neurodegeneration, 1995, 4(3): 271-281.
[8] Jackson-Lewis V, Przedborski S.Protocol for the MPTP mouse model of parkinson's disease[J]. Nature Protocols, 2007, 2(1): 141-151.
[9] Masato A, Plotegher N, Boassa D, et al.Impaired dopamine metabolism in Parkinson's disease pathogenesis[J]. Molecular Neurodegeneration, 2019, 14(1): 35.
[10] Marchitti SA, Deitrich RA, Vasiliou V.Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase[J]. Pharmacological Reviews, 2007, 59(2): 125-150.
[11] Lima Vanderlei de A, Do Nascimento LA, Eliezer D, et al. Role of Parkinson's disease-linked mutations and N-terminal acetylation on the oligomerization of α-synuclein induced by 3,4-dihydroxyphenylacetaldehyde[J]. ACS Chemical Neuroscience, 2019, 10(1): 690-703.
[12] Burke WJ, Li SW, Williams EA, et al.3,4-Dihydroxyphenylacetaldehyde is the toxic dopamine metabolite in vivo: implications for Parkinson's disease pathogenesis[J]. Brain Research, 2003, 989(2): 205-213.
[13] Goldstein DS, Sullivan P, Cooney A, et al.Vesicular uptake blockade generates the toxic dopamine metabolite 3,4-dihydroxyphenylacetal- dehyde in PC12 cells: relevance to the pathogenesis of Parkinson's disease[J]. Journal of Neurochemistry, 2012, 123(6): 932-943.
[14] Casida JE, Ford B, Jinsmaa Y, et al.Benomyl, aldehyde dehy- drogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease[J]. Chemical Research in Toxicology, 2014, 27(8): 1359-1361.
[15] Goldstein DS.The catecholaldehyde hypothesis: where MAO fits in[J]. Journal of Neural Transmission, 2020, 127(2): 169-177.

MPTP诱导野生型和A53T转基因型小鼠帕金森病模型纹状体中神经递质变化

Changes of Neurotransmitters in the Striatum of MPTP-induced Wild-type and A53T Transgenic Mouse Parkinson's Disease Models

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 9

编辑推荐

Metrics

[1]	马一丹, 沈鑫, 杨珺, 闫加庆. NLRP3炎症小体在神经退行性疾病及其治疗中的作用研究进展[J]. 中国药物警戒, 2023, 20(11): 1316-1320.
[2]	温路, 王硕, 张程璐, 陈乃宏, 苑玉和. MPTP诱导帕金森病小鼠胃肠道中单胺类递质及胶质细胞变化[J]. 中国药物警戒, 2021, 18(4): 320-323.
[3]	韩奇文, 温路, 陈乃宏, 苑玉和. A53T转基因小鼠体内α-突触核蛋白改变研究[J]. 中国药物警戒, 2021, 18(4): 312-314.
[4]	韩奇文, 陈颖, 陈乃宏, 苑玉和. MPTP诱导小鼠肝脏帕金森病样病理变化研究[J]. 中国药物警戒, 2021, 18(4): 306-311.
[5]	薄茹雪, 陈乃宏, 苑玉和. 少突胶质细胞在帕金森病中的研究进展[J]. 中国药物警戒, 2021, 18(4): 301-305.
[6]	周甜甜, 张秋双, 陈颖, 朱承根, 石建功, 陈乃宏, 苑玉和. 天麻联苄化合物20C对MPTP/p诱导帕金森病小鼠模型的作用及机制[J]. 中国药物警戒, 2020, 17(11): 753-757.
[7]	刘潜, 侯金凤, 张金兰, 张丹, 鲍秀琦, 孙华. 帕金森病细胞旁路开放对FLZ体外跨血脑屏障模型转运特性的影响[J]. 中国药物警戒, 2018, 15(1): 6-11.
[8]	张秋双, 陈颖, 陈乃宏, 苑玉和. 鱼藤酮诱导大鼠帕金森样损伤及其机制的研究[J]. 中国药物警戒, 2017, 14(9): 513-517.
[9]	刘霄, 邓毅. 左旋多巴诱导运动波动的预防及治疗进展[J]. 中国药物警戒, 2017, 14(1): 36-39.