pBDNF过表达对转基因阿尔茨海默病鼠学习记忆功能的影响

许曼玉; 张园; 易旭; 许志强

doi:10.16016/j.1000-5404.202011150

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pBDNF过表达对转基因阿尔茨海默病鼠学习记忆功能的影响

神经科学 | 更新时间：2026-01-09

- pBDNF过表达对转基因阿尔茨海默病鼠学习记忆功能的影响
- Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice
- 第三军医大学学报 2021年43卷第7期页码：629-634
- 作者机构：
  
  400042 重庆，陆军军医大学（第三军医大学）大坪医院神经内科
- 作者简介：
  
  [ 许志强，E-mail：xzq881@163.com XU Zhiqiang E-mail: xzq881@163.com
- 基金信息：
  
  重庆市自然科学基金(CSTC2018jcyjAX0664)
- DOI：10.16016/j.1000-5404.202011150
  中图分类号： R338.64;R341;R745.7
- 收稿：2020-11-17，
  
  修回：2020-12-19，
  
  纸质出版：2021-04-15
- 稿件说明：
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许曼玉, 张园, 易旭, 等. pBDNF过表达对转基因阿尔茨海默病鼠学习记忆功能的影响[J]. 第三军医大学学报, 2021,43(7):629-634.

Manyu XU, Yuan ZAHNG, Xu YI, et al. Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice[J]. Journal of Third Military Medical University, 2021, 43(7): 629-634.
许曼玉, 张园, 易旭, 等. pBDNF过表达对转基因阿尔茨海默病鼠学习记忆功能的影响[J]. 第三军医大学学报, 2021,43(7):629-634. DOI： 10.16016/j.1000-5404.202011150.

Manyu XU, Yuan ZAHNG, Xu YI, et al. Exogenetic over-expression of pBDNF affects learning and memory in APPswePS1dE9 transgenic mice[J]. Journal of Third Military Medical University, 2021, 43(7): 629-634. DOI： 10.16016/j.1000-5404.202011150.

摘要

目的

探讨海马注射携带脑源性神经营养因子前肽（pBDNF）基因的腺相关病毒基因整合载体（AAV-pBDNF）对阿尔茨海默病鼠（AD鼠）学习记忆功能的影响及可能机制。

方法

选用18只6月龄APP/PS1转基因AD小鼠，采用抛硬币法随机分为空载体对照组、AAV-pBDNF组、AAV-pBDNF+p75NTR抗体组，每组6只。空载体对照组右侧海马注射AAV-GFP（2 μL，1×10

vg/mL），AAV-pBDNF组右侧海马注射AAV-pBDNF（2 μL，1×10

vg/mL），AAV-pBDNF+p75NTR抗体组右侧海马注射AAV-pBDNF（2 μL，1×10

vg/mL）和p75NTR抗体（2 μL，10 μg/mL）。海马注射4周后行Morris水迷宫实验检测AD鼠学习记忆能力的变化。免疫荧光检测AAV-pBDNF在AD鼠脑内转染情况。Western blot检测海马突触后致密蛋白-95（postsynaptic density protein 95

PSD-95）的表达。

结果

水迷宫实验结果显示：各组小鼠的运动速度无明显差异。第5天时，对照组与AAV-pBDNF+p75NTR抗体组小鼠的逃避潜伏期均较第1天有明显下降（

0.05），而AAV-pBDNF组AD鼠的逃避潜伏期虽然也较第1天有所缩短，但差异无统计学意义。AAV-pBDNF组AD小鼠穿越平台次数较其余两组少（

0.05）。免疫荧光检测结果发现：AAV-pBDNF转染之后，在脑内神经元成功表达pBDNF，而胶质细胞不表达pBDNF。Western blot结果显示：AAV-pBDNF组AD鼠的PSD-95表达量低于对照组和AAV-pBDNF+p75NTR抗体组（

0.05）。

结论

pBDNF可能通过p75NTR受体信号通路下调海马PSD-95的表达，降低AD鼠的学习记忆能力。

Abstract

Objective

To explore the effect and possible machanism of recombinant adeno-associated virus (rAAV) vector containing brain-derived neurotrophic factor propeptide (AAV-pBDNF) on learning and memory in APPswePS1dE9 transgenic mice (Alzheimer's disease

AD).

Methods

A total of 18 APPswePS1dE9 transgenic mice were randomly and equally divided into co

ntrol group

AAV-pBDNF group and AAV-pBDNF+p75NTR antibody group. Recombinant AAV-pBDNF vector (2 μL

1×10

vg/mL) were stereotaxically injected into the right side of the hippocampus in AAV-pBDNF group

AAV-GFP (2 μL

1×10

vg/mL) into that of the control group

and same amount of AAV-pBDNF and p75NTR antibody (2 μL

10 μg/mL) into that of the AAV-pBDNF+p75NTR antibody group. There were 6 mice in each group. Morris water maze test was performed in 4 weeks after hippocampal injection to detect the changes of learning and memory abilities in AD rats. Immunofluorescence assay was used to observe the transfection ofAAV-pBDNF in the brain. Western blotting was employed to measure the expression of postsynaptic density protein 95 (PSD-95) in the hippocampus.

Results

The results of Morris water maze showed that no significant difference was seen in the movement speed of each group (

0.05); the escape incubation period on day 5 in the control group and AAV-pBDNF+p75NTR antibody group was significantly shorter than that of day 1 (

0.05); similar result was seen in the pBDNF group though no statistical difference (

0.05); and less platforms were crossed in the AD mice of the pBDNF group than those in the other 2 groups on day 6 in space exploration experiment (

0.05). Immunofluorescence assay showed that after transfection

pBDNF was expressed in the neurons

but not glial cells in the hippocampus. Western blotting results indicated that the expression of PSD-95 was obviously lower in the AAV-pBDNF group than the other 2 groups (

0.05).

Conclusion

pBDNF inhibits the learning and memory abilities of AD mice by down-regulating hippocampal expression of PSD-95.

关键词

Keywords

references

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