Changes of synapse-related proteins in the brain of 7-month-old and 16-month-old APP/PS1/tau transgenic mice and the effects of cornel iridoid glycoside on the AD model

doi:10.3969/j.issn.1006-7795.2020.03.014

Journal of Capital Medical University ›› 2020, Vol. 41 ›› Issue (3): 391-396.doi: 10.3969/j.issn.1006-7795.2020.03.014

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Changes of synapse-related proteins in the brain of 7-month-old and 16-month-old APP/PS1/tau transgenic mice and the effects of cornel iridoid glycoside on the AD model

Yang Cuicui, Bao Xunjie, Zhang Li, Li Yali, Li Lin, Zhang Lan

Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing Engineering Research Center for Nerve System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of Ministry of Education, Beijing 100053, China

Received:2020-02-29 Online:2020-06-21 Published:2020-06-17
Supported by:
This study was supported by National Natural Science Foundation of China (81874351,81703729), Natural Science Foundation of Beijing (7164315),Beijing High-level Health and Technical Personal Plan (2014-2-014).

Abstract

Abstract: Objective To explore the changes of memory ability and synapse-related proteins along with their influencing factors in the brain of APP/PS1/tau(3×Tg)transgenic mice of 7 and 16-month old, and to study the effect of cornel iridoid glycoside (CIG) on synapse-associated proteins in the brain of model mice. Methods 3×Tg mice of 7-month-old and 16-month-old were both treated with CIG for 2 months. New object recognition test was used to detect the ability of learning and memory in 3×Tg mice. Western blotting was used to observe the expression of synapsin-1, synaptophysin, synaptotagmin, amyloid precurson protein (APP), recombinant a disintegrin and metalloprotease 10(ADAM10), β-site APP-cleaving enzyme 1 (BACE1), presenilin-1(PS1), insulin degrading enzyme (IDE), and tau phosphorylation at Thr212 and Thr217. Results Compared to control group, 7-month-old 3×Tg mice had no change in the discrimination index, expression of synapsin-1, synaptophysin and synaptotagmin in cortex, while 16-month-old 3×Tg mice showed lower discrimination index and less expression of synapsin-1. After treatment, 16-month-old 3×Tg mice showed higher discrimination index and more expression of synapsin-1. Compared to control group, 7-month-old 3×Tg mice showed a similar level of APP, ADAM10, BACE1, PS1, and IDE in the brain. Conclusion Synapse-associated proteins are differentially expressed in the brains of 3×Tg mice at different ages. CIG has distinct effects on the expression of synapse-related proteins and memory ability in the brains of 3×Tg mice at different ages.

Key words: Alzheimer's disease, cornel iridoid glycoside, APP/PS1/tau, synaptic protein

CLC Number:

R743

Yang Cuicui, Bao Xunjie, Zhang Li, Li Yali, Li Lin, Zhang Lan. Changes of synapse-related proteins in the brain of 7-month-old and 16-month-old APP/PS1/tau transgenic mice and the effects of cornel iridoid glycoside on the AD model[J]. Journal of Capital Medical University, 2020, 41(3): 391-396.

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References

[1] Ferri C P, Prince M, Brayne C, et al. Global prevalence of dementia:a Delphi consensus study[J]. Lancet, 2005, 366(9503):2112-2117.
[2] Chan K Y, Wang W, Wu J J, et al. Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990-2010:a systematic review and analysis[J]. Lancet, 2013, 381(9882):2016-2023.
[3] Li W, Yu J, Liu Y, et al. Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer inverted question marks disease mouse model[J]. Mol Brain, 2014, 7(1):65.
[4] Louise W. Treatment for Alzheimer's disease:has anything changed?[J]. Aust Prescr, 2015, 38(2):60-63.
[5] 刘鹏, 朱琳, 纪雪飞, 等. 文冠果壳苷对APP/PS1转基因小鼠突触可塑性的作用及其机制研究[J]. 神经药理学报, 2017, 7(2):37.
[6] Chiara C, Carlotta F, Elisa C, et al. Synaptic dysfunction in alzheimer's disease and glaucoma:from common degenerative mechanisms toward neuroprotection[J]. Front Cell Neurosci, 2017,11:53.
[7] 杨翠翠,包训杰,张丽,等. 山茱萸环烯醚萜苷对APP/PS1/Tau三转基因小鼠脑内病理变化的影响[J]. 首都医科大学学报,2019, 40(4):588-595.
[8] Cees M, Verwey N A, Van d F W M, et al. Amyloid-β(1-42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease[J]. Clin Chem, 2009, 56(2):248-253.
[9] Xylaki1 M, Atzler1 B, Outeiro T F. Epigenetics of the synapse in neurodegeneration[J]. Curr Neurol Neurosci Rep, 2019, 19(10):72.
[10] 王丽, 焦劲松, 刘尊敬, 等. APP/PS-1/tau三转基因阿尔茨海默病模型小鼠早期认知功能研究[J]. 中国现代神经疾病杂志, 2015,15(5):406-410.
[11] Reddy P H, Mani G, Park B S, et al. Differential loss of synaptic proteins in Alzheimer's disease:implications for synaptic dysfunction[J]. J Alzheimers Dis, 2005, 7(2):103-117.
[12] Leuba G, Walzer C, Vernay A, et al. Postsynaptic density protein PSD-95 expression in Alzheimer's disease and okadaic acid induced neuritic retraction[J]. Neurobiol Dis, 2008, 30(3):408-419.
[13] Koffie R M, Hyman B T, Spires-Jones T L. Alzheimer's disease:synapses gone cold[J]. Mol Neurodegener, 2011, 6(1):63.
[14] Song S H, Augustine G J. Synapsin isoforms and synaptic vesicle trafficking[J]. Mol Cells, 2015, 38(11):936-940.
[15] Gouras G K. Aβ42 and tau pathologies are related and begin at synapses[J]. Alzheimer's Dement, 2010, 6(4):S148-S148.
[16] Song J M, DiBattista A M, Sung Y M, et al. A tetra(ethylene glycol) derivative of benzothiazole aniline ameliorates dendritic spine density and cognitive function in a mouse model of Alzheimer's disease[J]. Exp Neurol, 2014, 252:105-113.
[17] Ye M, Chung H, An Y H, et al. Standardized herbal formula PM012 decreases cognitive impairment and promotes neurogenesis in the 3×Tg AD mouse model of Alzheimer's disease[J]. Mol Neurobiol, 2016, 53(8):5401-5412.
[18] Ye M, Moon J, Yang J, et al. The standardized Lycium chinense fruit extract protects against Alzheimer's disease in 3xTg-AD mice[J]. J Ethnopharmacol, 2015, 172:85-90.
[19] 王利利, 纳鑫, 朱小南, 等. Tau/APP/PS1三转基因小鼠模型的建立及生物学特征[J]. 中国应用生理学杂志, 2012, 28(4):294-297.
[20] Jankowsky J L, Zheng H. Practical considerations for choosing a mouse model of Alzheimer's disease[J]. Mol Neurodegener, 2017, 12(1):89.
[21] Cortès-Saladelafont E, Lipstein N, García-Cazorla À. Presynaptic disorders:a clinical and pathophysiological approach focused on the synaptic vesicle[J]. J Inherit Metab Dis, 2018, 41(4):1-15.
[22] 曹君利, 丁海雷, 杨国栋, 等. 囊泡胞吐机制及与其相关的神经元可塑性[J]. 生命科学, 2003,15(5):283-288.
[23] 张拯,杨娟娇,孙琪,等.不同强度电针治疗对血管性痴呆大鼠学习记忆功能及海马CA1区β淀粉样蛋白1-40表达的影响[J].中国脑血管病杂志,2017,14(6):321-325.
[24] Mirza, F J, Zahid, S. The role of synapsins in neurological disorders[J]. Neurosci Bull, 2017, 34(2):349-358.

Changes of synapse-related proteins in the brain of 7-month-old and 16-month-old APP/PS1/tau transgenic mice and the effects of cornel iridoid glycoside on the AD model

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