山茱萸环烯醚萜苷对快速老化小鼠行为学及病理学改变的影响

doi:10.3969/j.issn.1006-7795.2021.05.010

首都医科大学学报 ›› 2021, Vol. 42 ›› Issue (5): 754-760.doi: 10.3969/j.issn.1006-7795.2021.05.010

• 神经精神疾病的中药治疗 • 上一篇下一篇

山茱萸环烯醚萜苷对快速老化小鼠行为学及病理学改变的影响

马登磊¹, 李延峥^1,2, 祝艳秋¹, 李林¹, 张兰^1*

1.首都医科大学宣武医院药学部神经变性病教育部重点实验室北京市神经药物工程研究中心,北京 100053;
2.华北理工大学附属医院神经内科,河北唐山 063000

收稿日期:2021-07-16 发布日期:2021-10-29
通讯作者: 国家自然科学基金(81874351,81673406),首都医科大学科研培育项目(PYZ19134),北京市科协青年人才托举计划(2020-2022),北京市金桥种子工程项目(ZZ21045),首都科技领军人才培养工程(Z191100006119017),北京市医院管理中心“登峰”计划专项(DFL20190803)。

Effects of cornel iridoid glycoside on the behavioral and pathological changes on senescence-accelerated mouse prone 8

Ma Denglei¹, Li Yanzheng^1,2, Zhu Yanqiu¹, Li Lin¹, Zhang Lan^1*

1. Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing Engineering Research Center for Nerve System Drugs, Beijing 100053, China;
2. Department of Neurology, Affiliated Hospital of North China University of Technology, Tangshan 063000, Hebei Province, China

Received:2021-07-16 Published:2021-10-29
Contact: National Natural Science Foundation of China (81874351, 81673406), Cultivation Fund of Capital Medical University (PYZ19134), Youth Foundation of Beijing Association for Science and Technology(2020-2022), Beijing Golden-bridge Project(ZZ21045), Capital Science and Technology Leading Talent Training Project (Z191100006119017), Beijing Hospitals Authority Ascent Plan (DFL20190803).

摘要/Abstract

摘要： 目的研究山茱萸环烯醚萜苷(cornel iridoid glycoside,CIG)对快速老化小鼠(senescence-accelerated mouse prone 8,SAMP8)的行为学表现及阿尔茨海默病相关病理学改变的影响。方法应用8月龄的SAMP8小鼠及正常老化小鼠(senescence accelerated mouse/resistant 1,SAMR1)作为对照小鼠,灌胃给予药物CIG处理。2个月后,应用自主活动仪观察小鼠的自主活动能力,避暗试验检测小鼠的被动回避记忆能力。应用Western blotting法分别检测小鼠脑内淀粉样前体蛋白(amyloid precursor protein,APP)代谢相关蛋白及突触相关蛋白的变化。结果与对照小鼠相比,SAMP8小鼠的自主活动次数及避暗试验中的步入潜伏期均显著降低,而CIG给药可以显著改善以上行为学表现,增强其自主活动和记忆能力。进一步机制研究发现,CIG可以增加SAMP8小脑内去整合素金属蛋白酶10 (a disintegrin and metalloproteinase 10,ADAM10)和胰岛素降解酶(insulin-degrading enzyme,IDE)的表达,增加可溶性淀粉样前体蛋白α(soluble amyloid procurer protein α,sAPPα)的表达,同时增加了突触相关蛋白synaptophysin、PSD95、GluR1和p-CaMKIIα的表达。结论 CIG可以用于改善老化引起的认知障碍及阿尔茨海默病样的病理改变。

关键词: 山茱萸环烯醚萜苷, 老化, 阿尔茨海默病, SAMP8小鼠, 淀粉样前体蛋白, 突触

Abstract: Objective To investigate the effects of cornel iridoid glycoside (CIG) on cognitive behavioral and Alzheimer's-like pathological changes in senescence-accelerated mouse prone 8 (SAMP8) mice. Methods The drug of CIG was chronically administered with intragastric injection to 8-month-old SAMP8 mice and senescence accelerated mouse/resistant 1 (SAMR1) mice in the control for two months. The locomotor activity was tested by the locomotor activity system. The passive avoidance memory function was measured by step through test. The Western blotting was used to detect the expression of amyloid precursor protein amyloid precursor protein (APP) and synapse associated protein. Results The results showed that SAMP8 mice exhibited impaired locomotor activity and cognition. Intragastric administration of CIG for 2 months obviously improved the locomotor activity and cognitive function of SAMP8 mice. CIG treatment elevated the levels of soluble APPα fragment, a disintegrin and metalloproteinase 10 (ADAM10) and insulin-degrading enzyme (IDE). Moreover, CIG increased the expression of synaptophysin, postsynaptic density protein 95, AMPA receptor subunit 1 and phosphorylation of calmodulin dependent protein kinase IIα (CaMKIIα). Conclusion CIG may be beneficial to treating the aging induced cognitive impairment and Alzheimer's-like pathological changes.

Key words: cornel iridoid glycoside, aging, Alzheimer's disease, SAMP8 mice, amyloid precursor protein, synapse

中图分类号:

R745.1

马登磊, 李延峥, 祝艳秋, 李林, 张兰. 山茱萸环烯醚萜苷对快速老化小鼠行为学及病理学改变的影响[J]. 首都医科大学学报, 2021, 42(5): 754-760.

Ma Denglei, Li Yanzheng, Zhu Yanqiu, Li Lin, Zhang Lan. Effects of cornel iridoid glycoside on the behavioral and pathological changes on senescence-accelerated mouse prone 8[J]. Journal of Capital Medical University, 2021, 42(5): 754-760.

参考文献

[1] Sengoku R. Aging and Alzheimer's disease pathology[J]. Neuropathology, 2020, 40(1): 22-29.
[2] Xia X, Jiang Q, McDermott J, et al. Aging and Alzheimer's disease: comparison and associations from molecular to system level[J]. Aging Cell, 2018, 17(5): e12802.
[3] Liu B, Liu J, Shi J S. SAMP8 mice as a model of age-related cognition decline with underlying mechanisms in Alzheimer's disease[J]. J Alzheimers Dis, 2020,75(2):385-395.
[4] Akiguchi I, Pallàs M, Budka H, et al. SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions[J]. Neuropathology, 2017,37(4):293-305.
[5] 马登磊,张旭,张丽,等. 山茱萸环烯醚萜苷对创伤性脑损伤大鼠认知功能及tau蛋白磷酸化的影响[J]. 首都医科大学学报,2020,41(3): 397-402.
[6] Ma D, Zhu Y, Li Y, et al. Beneficial effects of cornel iridoid glycoside on behavioral impairment and senescence status in SAMP8 mice at different ages[J]. Behav Brain Res, 2016, 312: 20-29.
[7] Ma D, Li Y, Zhu Y, et al. Cornel iridoid glycoside ameliorated Alzheimer's disease-like pathologies and necroptosis through RIPK1/MLKL pathway in young and aged SAMP8 mice[J]. Evid Based Complement Alternat Med, 2021, 2021: 9920962.
[8] 马登磊,张兰,李林. 脑外伤动物模型认知障碍评价方法研究进展[J]. 中国康复理论与实践,2015,21(1): 65-68.
[9] Akiguchi I, Pallàs M, Budka H, et al. SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions[J]. Neuropathology, 2017, 37(4): 293-305.
[10]Wang F, Chen H, Sun X. Age-related spatial cognitive impairment is correlated with a decrease in ChAT in the cerebral cortex, hippocampus and forebrain of SAMP8 mice[J]. Neurosci Lett, 2009, 454(3): 212-217.
[11]Zhang Z, Yang J, Liu C, et al. Pseudoginsenoside-F11 alleviates cognitive deficits and Alzheimer's disease-type pathologies in SAMP8 mice[J]. Pharmacol Res, 2019, 139:512-523.
[12]Del V J, Duran-Vilaregut J, Manich G, et al. Early amyloid accumulation in the hippocampus of SAMP8 mice[J]. J Alzheimers Dis, 2010, 19(4): 1303-1315.
[13]Huang J, Wu D, Wang J, et al. Effects of Panax notoginseng saponin on α, β, and γ secretase involved in Aβ deposition in SAMP8 mice[J]. NeuroReport, 2014, 25(2): 89-93.
[14]Puigoriol-Illamola D, Leiva R, Vázquez-Carrera M, et al. 11β-HSD1 inhibition rescues samp8 cognitive impairment induced by metabolic stress[J]. Mol Neurobiol, 2020, 57(1):551-565.
[15]Kitaoka K, Shimizu N, Ono K, et al. The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice[J]. Neuropharmacology, 2013, 72: 58-65.
[16]Kurochkin I V, Guarnera E, Berezovsky I N. Insulin-degrading enzyme in the fight against Alzheimer's disease[J]. Trends Pharmacol Sci, 2018, 39(1): 49-58.
[17]Rajmohan R, Reddy P H. Amyloid-Beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer's disease neurons[J]. J Alzheimers Dis, 2017, 57(4): 975-999.
[18]Lian W W, Zhou W, Zhang B Y, et al. DL0410 ameliorates cognitive disorder in SAMP8 mice by promoting mitochondrial dynamics and the NMDAR-CREB-BDNF pathway[J]. Acta Pharmacol Sin, 2021,42(7):1055-1068.
[19]Harris K P, Littleton J T. Transmission, development, and
plasticity of synapses[J]. Genetics, 2015, 201(2): 345-375.
[20]Diering G H, Huganir R L. The AMPA receptor code of synaptic plasticity[J]. Neuron, 2018, 100(2): 314-329.
[21]Zalcman G, Federman N, Romano A. CaMKII isoforms in learning and memory: localization and function[J]. Front Mol Neurosci, 2018, 11:445.
[22]Cai Q, Zeng M, Wu X, et al. CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation[J]. Cell Res, 2021, 31(1): 37-51.
[23]曹丽,石岩硕,庞国勋.谷氨酰胺在神经系统疾病的临床应用研究进展[J].解放军医药杂志,2020,32(6):113-116.

山茱萸环烯醚萜苷对快速老化小鼠行为学及病理学改变的影响

Effects of cornel iridoid glycoside on the behavioral and pathological changes on senescence-accelerated mouse prone 8

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