Neuroprotective Effect of Tetrahydroxy Stilbene Glucoside on Aβ<sub>25-35</sub>-induced Neuron Synapses via CREB/BDNF Signaling Pathway

Yu-hui YAN; Meng ZHU; Hong-yan LI; Ying-bo LU

doi:10.13422/j.cnki.syfjx.20191736

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Neuroprotective Effect of Tetrahydroxy Stilbene Glucoside on Aβ_25-35-induced Neuron Synapses via CREB/BDNF Signaling Pathway

Pharmacology | 更新时间：2021-02-09

- Neuroprotective Effect of Tetrahydroxy Stilbene Glucoside on Aβ_25-35-induced Neuron Synapses via CREB/BDNF Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 17, Pages: 50-56(2019)
- 作者机构：
  
  1.江苏食品药品职业技术学院，江苏　淮安　 223003；
  2.辽宁中医药大学，辽宁　大连　 116600
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191736
  CLC： R2-0; R285.5; R246.6
- Received：15 January 2019，
  
  Published Online：17 May 2019，
  
  Published：05 September 2019
- 稿件说明：
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Yu-hui YAN, Meng ZHU, Hong-yan LI, et al. Neuroprotective Effect of Tetrahydroxy Stilbene Glucoside on Aβ_25-35-induced Neuron Synapses via CREB/BDNF Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 50-56.
DOI：

Yu-hui YAN, Meng ZHU, Hong-yan LI, et al. Neuroprotective Effect of Tetrahydroxy Stilbene Glucoside on Aβ_25-35-induced Neuron Synapses via CREB/BDNF Signaling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 50-56. DOI： 10.13422/j.cnki.syfjx.20191736.

摘要

目的：

研究中药何首乌有效成分二苯乙烯苷(TSG)对

-淀粉样蛋白25-35(A

25-35

)损伤的小鼠海马神经元的保护作用，并探讨其可能的作用机制。

方法：

小鼠海马神经元细胞分离自新生48 h内胎鼠大脑海马，培养9 d待神经元成熟后，采用免疫荧光法对其进行鉴定。将培养成熟的神经元细胞分为正常组、模型组(A

25-35

孵育造模)和TSG组(A

25-35

孵育造模后，分别加入TSG 6.25，12.5，25，50，100 μmol·L

－1

)。细胞增殖毒性检测(CCK-8)试剂盒和乳酸脱氢酶(LDH)法检测各组细胞活性，免疫荧光法检测突触素-1(SYN-1)蛋白的表达，酶联免疫吸附测定(ELISA)检测突触后膜致密蛋白-95(PSD-95)和突触体素(SYP)的含量，逆转录-聚合酶链式反应(RT-PCR)检测环磷酸腺苷反应元件结合蛋白(CREB)和脑源性神经营养因子(BDNF)mRNA的表达，免疫荧光法和蛋白免疫印迹法(Western blot)检测CREB，磷酸化CREB(p-CREB)和BDNF蛋白的表达。

结果：

与正常组比较，模型组细胞存活率显著降低，LDH释放量显著增高(

0.01)，SYN-1，PSD-95和SYP的含量明显降低(

0.05，

0.01)，p-CREB和BDNF mRNA及蛋白的表达明显下调(

0.05，

0.01)；与模型组比较，不同浓度TSG均可提高细胞存活率，降低LDH释放量(

0.05，

0.01)，TSG对A

25-35

造模的小鼠海马神经元细胞的最适治疗浓度为25 μmol·L

－1

；25 μmol·L

－1

TSG能够显著增强SYN-1的表达量(

0.01)，明显提高PSD-95和SYP的含量(

0.05)；上调p-CREB和BDNF mRNA及蛋白的表达(

0.05，

0.01)，但对CREB mRNA及蛋白的表达无显著影响。

结论：

TSG对A

25-35

损伤的小鼠海马神经元突触具有保护作用，其机制可能与促进CREB的磷酸化使p-CREB表达增多，并促进神经营养因子BDNF的释放有关。

Abstract

Objective:

To investigate the neuroprotective effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on

-amyloid protein 25-35 (A

25-35

)-induced neuron synapses damage.

Method:

Primary neurons were isolated and purified from cerebral cortex of suckling mouse. Then neurons were divided into control group

model group (incubation with A

25-35

) and TSG groups (after incubation with A

25-35

add 6.25

12.5

100 μmol·L

-1

TSG). Cell counting kit-8 (CCK-8) and Lactate dehydrogenase (LDH) methods were used to observe the viability of neuron

immunocytochemical staining was performed to determine the expressions of synapsin-1 (SYN-1)

and the concentration of postsynaptic density-95 (PSD-95) and synaptophysin (SYP) were detected by enzyme-linked immunosorbent assay (ELISA) method. The level of cyclic adenosine monophosphate response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR) and the level of CREB

Phosphorylated CREB (p-CREB) and BDNF proteins were determined by immunocytochemical staining or Western blot (WB).

Result:

Compared with normal group

the cell survival rate of model group was significantly reduced

LDH release was significantly increased (

0.01)

and the expressions of SYN-1

PSD-95 and SYP were significantly decreased (

0.05

0.01). The expressions of p-CREB and BDNF mRNA and protein were significantly down-regulated (

0.05

0.01). Compared with model group

different concentrations of TSG could increase cell viability and reduce LDH release (

0.05

0.01)

the optimal therapeutic concentration of TSG is 25 μmol·L

-1

25 μmol·L

-1

TSG can significantly enhance the expression of SYN-1(

0.01)

increased the concentration of PSD-95 and SYP (

0.05)

up-regulated the mRNA expression of BDNF

and promoted the protein expression of p-CREB and BDNF (

0.05

0.01). There was no significant effect on the expression of CREB mRNA and protein.

Conclusion:

TSG possesses the neuroprotective effect on A

25-35

-induced neuron synapses

the mechanism may be associated with the activation of CREB/BDNF signaling pathway.

关键词

Keywords

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⁰

Neuroprotective Effect of Tetrahydroxy Stilbene Glucoside on Aβ25-35-induced Neuron Synapses via CREB/BDNF Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20191736

摘要

Abstract

关键词

Keywords

references

Neuroprotective Effect of Tetrahydroxy Stilbene Glucoside on Aβ_25-35-induced Neuron Synapses via CREB/BDNF Signaling Pathway