Study on effects of Tiaoxin Bushen Formula on improving synapse loss and tau hyperphosphory⁃lation in prefrontal cortex of Alzheimer’s disease mice

Zhiyuan LU; Baoqing WANG; Chenyi ZHAO; Guang YANG; Yuting TONG; Jianmei YANG; Ying XU

doi:10.16305/j.1007-1334.2022.2205067

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Study on effects of Tiaoxin Bushen Formula on improving synapse loss and tau hyperphosphory⁃lation in prefrontal cortex of Alzheimer’s disease mice

更新时间：2022-09-30

- Study on effects of Tiaoxin Bushen Formula on improving synapse loss and tau hyperphosphory⁃lation in prefrontal cortex of Alzheimer’s disease mice
- Shanghai Journal of Traditional Chinese Medicine Vol. 56, Issue 9, Pages: 76-81(2022)
- 作者机构：
  
  1.上海中医药大学基础医学院（上海 201203）
  2.复旦大学附属中山医院呼吸科（上海 200032）
  3.上海市徐汇区中心医院呼吸科（上海 200031）
  4.上海市徐汇区中心医院中医科（上海 200031）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2022.2205067
  CLC：
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卢志园,王葆青,赵晨怡等.调心补肾方改善阿尔茨海默病小鼠前额皮质突触缺失和tau蛋白过度磷酸化的作用研究[J].上海中医药杂志,2022,56(09):76-81.

LU Zhiyuan,WANG Baoqing,ZHAO Chenyi,et al.Study on effects of Tiaoxin Bushen Formula on improving synapse loss and tau hyperphosphory⁃lation in prefrontal cortex of Alzheimer’s disease mice[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(09):76-81.
卢志园,王葆青,赵晨怡等.调心补肾方改善阿尔茨海默病小鼠前额皮质突触缺失和tau蛋白过度磷酸化的作用研究[J].上海中医药杂志,2022,56(09):76-81. DOI： 10.16305/j.1007-1334.2022.2205067.

LU Zhiyuan,WANG Baoqing,ZHAO Chenyi,et al.Study on effects of Tiaoxin Bushen Formula on improving synapse loss and tau hyperphosphory⁃lation in prefrontal cortex of Alzheimer’s disease mice[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(09):76-81. DOI： 10.16305/j.1007-1334.2022.2205067.

摘要

目的,2,研究调心补肾方（TXBSF）对早老素1/2条件性双基因敲除（PS cDKO）的阿尔茨海默病（AD）小鼠模型前额皮质（PFC）突触缺失和tau蛋白过度磷酸化的影响。,方法,2,采用3～3.5月龄小鼠，雌雄各半，随机分为野生型组（WT）、PS cDKO模型组（cDKO）、PS cDKO+TXBSF组（cDKO+TXBSF），每组6只。WT和cDKO两组小鼠给予普通饲料，cDKO+TXBSF小鼠给予含TXBSF（给药剂量为2.55 g/kg）的饲料喂养，共治疗90 d。采用Western blot法检测小鼠PFC中N-甲基-D-天冬氨酸受体（NMDAR）亚基（NR1、NR2A、NR2B）、微管相关蛋白2（MAP2）和tau蛋白表达；qRT-PCR法检测小鼠PFC中,NR1、NR2A、NR2B,和,MAP2, mRNA表达。,结果,2,Western blot检测结果显示，与cDKO小鼠相比，cDKO+TXBSF小鼠PFC中NR1、NR2A、NR2B和MAP2蛋白表达增加（,P,<,0.05）；磷酸化tau（ser 396/404）蛋白表达减少（,P,<,0.05）。qRT-PCR结果显示，与cDKO小鼠相比，cDKO+TXBSF小鼠PFC中,NR1、NR2A、NR2B,和,MAP2, mRNA表达增加（,P,<,0.05）。,结论,2,TXBSF对PS cDKO小鼠记忆缺陷的改善作用可能通过逆转PFC的tau蛋白过度磷酸化和下调突触相关蛋白的表达来实现。

Abstract

Objective,2,To elucidate the beneficial effects of Tiaoxin Bushen Formula （TXBSF） on synapse loss and tau hyperphosphorylation in the prefrontal cortex （PFC） of Alzheimer’s disease （AD） model mice with presenilin 1/2 conditional double knockout （PS cDKO）.,Methods,2,Mice aged 3～3.5 months， half male and half female， were randomly divided into three groups： Wildtype group （WT， ,n,=6）， PS cDKO group （cDKO， ,n,=6）， and PS cDKO+TXBSF group （cDKO+TXBSF， ,n,=6）. The mice in the WT and cDKO groups were continuously fed with standard chow， and mice in cDKO+TXBSF group were fed with TXBSF （2.55 g/kg）. After 90 days of treatment， Western blot analysis was used to evaluate the protein expression levels of synapse-associated proteins in the PFC of mice， such as N-methyl-d-aspartate receptor （NMDAR） subunits （NR1， NR2A， NR2B）， Microtubule associated protein-2 （MAP2） and tau hyperphosphorylation； qRT-PCR was used to detect the mRNA levels of synapse-associated proteins in the PFC of mice， including ,NR1,，, NR2A,，, NR2B,， and ,MAP2,.,Results,2,Western blot results showed that compared with mice in cDKO group， mice in cDKO+TXBSF group had higher protein expression levels of synapse-related proteins （NR1， NR2A， NR2B and MAP2）（,P,<,0.05） and lower expression level of p-tau （ser 396/404）（,P,<,0.05）. The qRT-PCR analysis showed that compared with mice in cDKO group， mice in the cDKO+TXBSF group had higher mRNA levels of synapse-related proteins （,NR1,，, NR2A,，, NR2B,， and ,MAP2,） in the PFC of mice （,P,<,0.05）.,Conclusion,2,TXBSF has the potential to improve memory impairments in PS cDKO mice， which could be achieved by attenuating tau hyperphosphorylation and up-regulating expression of synaptic proteins in the PFC.

关键词

阿尔茨海默病调心补肾方前额皮质突触缺失tau蛋白小鼠模型中药研究

Keywords

Alzheimer’s diseaseTiaoxin Bushen Formulaprefrontal cortexsynapse losstau proteinmouse modeltraditional Chinese herbal medicine research

references

JIA J， WEI C， CHEN S， et al. The cost of Alzheimer’s disease in China and re-estimation of costs worldwide［J］. Alzheimers Dement， 2018， 14（4）： 483-491.

SCHELTENS P， DE STROOPER B， KIVIPELTO M， et al. Alzheimer’s disease［J］. Lancet， 2021， 397（10284）： 1577-1590.

林水淼，王健，周如倩，等. 从心肾论治阿尔茨海默病的临床效果（英文）［J］. 中国临床康复，2006， 10（11）： 162-164.

王健，王晓雯，邓海燕，等. 调心方对APP/PS1双转基因AD小鼠脑组织突触的保护作用［J］. 上海中医药杂志，2017， 51（4）： 95-98.

王迪霖，郎韫哲，袁见，等. 调心补肾方改善Presenilin1/2条件性双基因敲除小鼠记忆障碍的机制研究［J］. 世界科学技术-中医药现代化，2019， 21（9）： 1827-1834.

WANG Y， SHENG H， ZHAO J， et al. Changes in the prefrontal cortex after the hippocampus was injected with Aβ25-35 via the P35/P25-CDK5-Tau hyperphosphorylation signaling pathway［J］. Neurosci Lett， 2021， 741： 135453.

SAURA C A， CHOI S Y， BEGLOPOULOS V， et al. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration［J］. Neuron， 2004， 42（1）： 23-36.

ZHAO Y， DENG H， LI K， et al. Trans-cinnamaldehyde improves neuroinflammation-mediated NMDA receptor dysfunction and memory deficits through blocking NF-κB pathway in presenilin1/2 conditional double knockout mice［J］. Brain Behav Immun， 2019， 82： 45-62.

GAO J， WANG L， ZHAO C， et al. Peony seed oil ameliorates neuroinflammation-mediated cognitive deficits by suppressing microglial activation through inhibition of NF-κB pathway in presenilin 1/2 conditional double knockout mice［J］. J Leukoc Biol， 2021， 110（6）： 1005-1022.

DYER O. Long delayed publication of data on Alzheimer’s drug Aduhelm leaves questions unanswered［J］. BMJ， 2022， 376： o808.

林水淼，周如倩，王健，等. 调心方、补肾方对Alzheimer病患者认知功能和日常生活能力作用的比较研究［J］. 中国老年学杂志，2002， 11（6）： 434-436.

王健，林水淼. “心肾同治”阿尔茨海默病的思考［J］. 上海中医药杂志，2011， 45（9）： 22-23.

CALSOLARO V， EDISON P. Neuroinflammation in Alzheimer’s disease： Current evidence and future directions［J］. Alzheimers Dement， 2016， 12（6）： 719-732.

顾祎宁，卢志园，巴宗韬，等. 调心补肾方对阿尔茨海默病小鼠前额皮质中小胶质细胞激活和神经炎症反应的影响［J/OL］.上海中医药杂志，2022［2022-05-10］. https：//kns.cnki.net/kcms/detail/detail.aspx？dbcode=CAPJ&dbname=CAPJLAST&filename=SHZZ20220427000&uniplatform=NZKPT&v=xhvOrF1pwYAYFf1O89wDwCLTCc2tygY5mc5aVHKYJKYTrBN0elW4C3Wc3h8lO9sFhttps://kns.cnki.net/kcms/detail/detail.aspx?dbcode=CAPJ&dbname=CAPJLAST&filename=SHZZ20220427000&uniplatform=NZKPT&v=xhvOrF1pwYAYFf1O89wDwCLTCc2tygY5mc5aVHKYJKYTrBN0elW4C3Wc3h8lO9sF.

SZULE J A， JUNG J H， MCMAHAN U J. The structure and function of “active zone material” at synapses［J］. Biological sciences， 2015， 370（1672）： 20140189.

MATTSON M P， MAGNUS T. Ageing and neuronal vulnerability［J］. Nat Rev Neurosci， 2006， 7（4）： 278-294.

PAGANO J， GIONA F， BERETTA S， et al. N-methyl-d-aspartate receptor function in neuronal and synaptic development and signaling［J］. Curr Opin Pharmacol， 2021， 56： 93-101.

KADAVATH H， HOFELE R V， BIERNAT J， et al. Tau stabilizes microtubules by binding at the interface between tubulin heterodimers［J］. Proc Natl Acad Sci U S A， 2015， 112（24）： 7501-7506.

GORANTLA N V， CHINNATHAMBI S. Autophagic pathways to clear the tau aggregates in Alzheimer’s disease［J］. Cell Mol Neurobiol， 2021， 41（6）： 1175-1181.

GRUBISHA M J， SUN X， MACDONALD M L， et al. MAP2 is differentially phosphorylated in schizophrenia， altering its function［J］. Mol Psychiatry， 2021， 26（9）： 5371-5388.

DONG Z， YAN L， HUANG G， et al. Ibuprofen partially attenuates neurodegenerative symptoms in presenilin conditional double-knockout mice［J］. Neuroscience， 2014， 270： 58-68.

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