Effects of cornel iridoid glycoside on Alzheimer's disease-associated neuropathology in APP/PS1/Tau transgenic mice

doi:10.3969/j.issn.1006-7795.2019.04.018

Abstract

Abstract: Objective To observe the effects of Cornel iridoid glycoside (CIG) on pathology in the brain of 3×Tg mice. Methods The APP/PS1/Tau (3×Tg) mice were intragastrically administered with CIG (100 mg/kg, 200 mg/kg) once a day for 2 months. Congo red staining was used to observe the number and distribution of senile plaque in hippocampus. Western blotting was used to observe the expression of tau phosphorylation at Thr212 and Thr217. Immunohistochemistry and qRT-PCR were used to detect protein and transcription level of brain derived neurotrophic factor (BDNF). Nissl staining was used to observe the number of Nissl's body in hippocampus. Results Compared with the control group, the Aβ amyloid plaque deposition increased significantly in the 18-month-old model group, while 100 or 200 mg·kg^-1·d^-1 CIG treatment could reduce the plaque burden in the brain. The phosphorylation level of tau at Thr217 was significantly increased in the model group, while that at Thr212 was not significantly elevated. CIG treatment significantly antagonized the hyperphosphorylation of tau at Thr217. In the model group, the protein and mRNA levels of BDNF in hippocampus were decreased, and CIG could significantly restore the protein and mRNA levels of BDNF. CIG treatment could increase the number of Nissl's body in the brain. Conclusion CIG could reduce the deposition of Aβ in the brain, abnormal hyperphosphorylation of tau protein, restore the expression of BDNF in the brain, and protect neurons.

Key words: cornel iridoid glycoside, Aβ, Tau, brain derived neurotrophic factor (BDNF), Alzheimer's disease

CLC Number:

R592

Yang Cuicui, Bao Xunjie, Zhang Li, Li Yali, Li Lin, Zhang Lan. Effects of cornel iridoid glycoside on Alzheimer's disease-associated neuropathology in APP/PS1/Tau transgenic mice[J]. Journal of Capital Medical University, 2019, 40(4): 588-595.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2019.04.018

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2019/V40/I4/588

References 30

[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]	陈传锋,何承林,陈红霞,等. 我国老年痴呆研究概况[J]. 宁波大学学报:教育科学版,2012,34(2):45-50.
[3]	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.
[4]	Song Y,Wang J. Overview of Chinese research on senile dementia in mainland China[J]. Ageing Res Rev,2010,9 Suppl 1:S6-S12.
[5]	褚思娟,李林,张兰. 山茱萸环烯醚萜苷主要药理作用研究进展[C]. 2013年全国老年性痴呆与相关疾病学术会议,2013,2.
[6]	于淼,王晓先,贾琳. 山茱萸的药理作用研究进展[J]. 东南国防医药,2010,12(3):240-243.
[7]	Yang C C,Kuai X X,Li Y L,et al. Cornel iridoid glycoside attenuates tau hyperphosphorylation by inhibition of PP2A demethylation[J]. Evid Based Complement Alternat Med,2013,2013:108486.
[8]	褚燕琦,李玮,张兰,等. 山茱萸环烯醚萜苷对蛋白磷酸酶抑制剂冈田酸拟阿尔采末病细胞模型的作用[J]. 中国药理学通报,2006,8:960-963.
[9]	Zhao L H,Ding Y X,Zhang L,et al. Cornel iridoid glycoside improves memory ability and promotes neuronal survival in fimbria-fornix transected rats[J]. Eur J Pharmacol,2010,647(1-3):68-74.
[10]	丁月霞,张丽,叶翠飞,等. 山茱萸环烯醚萜苷对穹隆海马伞切断大鼠学习记忆能力和突触生长素的影响[J]. 中国新药杂志,2010,19(2):133-138.
[11]	丁月霞,张丽,叶翠飞,等. 山茱萸环烯醚萜苷对穹隆海马伞切断大鼠海马区神经元存活和细胞凋亡调控因子的影响[J]. 首都医科大学学报,2011,32(1):73-78.
[12]	Beeri M S,Sonnen J. Brain BDNF expression as a biomarker for cognitive reserve against Alzheimer disease progression[J]. Neurology,2016,86(8):702-703.
[13]	Ossenkoppele R,Smith R,Ohlsson T,et al. Associations between tau,abeta,and cortical thickness with cognition in alzheimer disease[J]. Neurology,2019,92(6):e601-e612.
[14]	于淼,王晓先. 山茱萸的药理作用研究进展[J]. 东南国防医药,2010,12(3):240-243,260.
[15]	杨明明,袁晓旭,赵桂琴,等. 山茱萸化学成分和药理作用的研究进展[J]. 承德医学院学报,2016,33(5):398-400.
[16]	Ye M,Chung H S,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.
[17]	Sabogal-Guaqueta A M,Osorio E,Cardona-Gomez G P. Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer's mice[J]. Neuropharmacology,2016,102:111-120.
[18]	Yang S H,Kim J,Lee M J,et al. Abnormalities of plasma cytokines and spleen in senile APP/PS1/Tau transgenic mouse model[J]. Sci Rep,2015,5:15703.
[19]	Heraud C,Goufak D,Ando K,et al. Increased misfolding and truncation of tau in APP/PS1/tau transgenic mice compared to mutant tau mice[J]. Neurobiol Dis,2014,62:100-112.
[20]	Yang J T,Wang Z J,Cai H Y,et al. Sex differences in neuropathology and cognitive behavior in APP/PS1/tau triple-transgenic mouse model of alzheimer's disease[J]. Neurosci Bull,2018,34(5):736-746.
[21]	谭龙,李海强,李宜波,等. APP/PS1双转基因小鼠的繁育、鉴定及评价[J]. 中国应用生理学杂志,2018,34(2):111-114.
[22]	Wang W,Lu L,Wu Q Q,et al. Brain amyloid-beta plays an initiating role in the pathophysiological process of the PS1V97L-Tg mouse model of alzheimer's disease[J]. J Alzheimers Dis,2016,52(3):1089-1099.
[23]	Kuznetsov I A,Kuznetsov A V. Simulating the effect of formation of amyloid plaques on aggregation of tau protein[J]. Proc Math Phys Eng Sci,2018,474(2220):20180511.
[24]	Miao J,Shi R,Li L,et al. Pathological tau from Alzheimer's brain induces site-specific hyperphosphorylation and SDS- and reducing agent-resistant aggregation of tau in vivo[J]. Front Aging Neurosci,2019,11:34.
[25]	Einoch R,Weinreb O,Mandiuk N,et al. The involvement of BDNF-CREB signaling pathways in the pharmacological mechanism of combined SSRI- antipsychotic treatment in schizophrenia[J]. Eur Neuropsychopharmacol,2017,27(5):470-483.
[26]	Kazim S F,Blanchard J,Dai C L,et al. Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease[J]. Neurobiol Dis,2014,71:110-130.
[27]	陈巍,杨潇,张凤暖,等. 健脾化痰活血方改善亚临床甲减大鼠认知能力及其可能机制[J]. 北京中医药大学学报,2018,41(11):918-927.
[28]	林蓁. 神经元尼氏小体改良染色[J]. 临床与实验病理学杂志,2008,24(6):742-743.
[29]	Ya B L,Li C Y,Zhang L,et al. Cornel iridoid glycoside inhibits inflammation and apoptosis in brains of rats with focal cerebral ischemia[J]. Neurochem Res, 2010,35(5):773-781.
[30]	Yao R Q,Zhang L,Wang W,et al. Cornel iridoid glycoside promotes neurogenesis and angiogenesis and improves neurological function after focal cerebral ischemia in rats[J]. Brain Res Bull, 2009,79(1):69-76.