Effects of AAV-proBDNF on hippocampal DCX positive cells and PSD-95 expression in Alzheimer's disease mice

Manyu XU; Jia CHEN; Zhiqiang XU

doi:10.16016/j.1000-5404.201808088

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Effects of AAV-proBDNF on hippocampal DCX positive cells and PSD-95 expression in Alzheimer's disease mice

Basic Medicine | 更新时间：2026-01-09

- Effects of AAV-proBDNF on hippocampal DCX positive cells and PSD-95 expression in Alzheimer's disease mice
- Journal of Third Military Medical University Vol. 41, Issue 2, Pages: 95-99(2019)
- 作者机构：
  
  400042 重庆，陆军军医大学(第三军医大学)第三附属医院(野战外科研究所)神经内科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81271411);the Natural Science Foundation of Chongqing(CSTC2018jcyjAX0664)
- DOI：10.16016/j.1000-5404.201808088
  CLC： R338.26; R394.3; R745.7
- Received：12 August 2018，
  
  Revised：2018-10-16，
  
  Published：30 January 2019
- 稿件说明：
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Manyu XU, Jia CHEN, Zhiqiang XU. Effects of AAV-proBDNF on hippocampal DCX positive cells and PSD-95 expression in Alzheimer's disease mice[J]. Journal of Third Military Medical University, 2019, 41(2): 95-99.
DOI：

Manyu XU, Jia CHEN, Zhiqiang XU. Effects of AAV-proBDNF on hippocampal DCX positive cells and PSD-95 expression in Alzheimer's disease mice[J]. Journal of Third Military Medical University, 2019, 41(2): 95-99. DOI： 10.16016/j.1000-5404.201808088.

摘要

目的

探讨侧脑室注射携带抗裂解脑源性神经营养因子前体(proBDNF)基因的腺相关病毒基因整合载体(AAV-proBDNF)对阿尔茨海默病小鼠(AD鼠)海马神经形成与生长的影响。

方法

取5月龄APP/PS1转基因AD鼠15只，采用抛硬币法随机分为正常对照组(

=5)、空载体对照组(

=5)和AAV-proBDNF组(

=5)，AAV-proBDNF组右侧侧脑室注射AAV-proBDNF(4 μL

2×10

v.g./mL)，空载体对照组右侧侧脑室注射等量空病毒载体，正常对照组右侧侧脑室注射生理盐水(4 μL)。于侧脑室注射后4周采用ELISA检测海马proBDNF含量，免疫组化检测海马齿状回DCX阳性细胞数，Western blot检测海马突触后致密物-95(PSD-95)表达。

结果

侧脑室注射后4周，AAV-proBDNF组脑内proBDNF表达水平较正常对照组明显增加，且显著高于空载体对照组，差异均具有统计学意义(

0.05)；AAV-proBDNF组海马DCX阳性细胞数为(202.46±24.27)，明显低于正常对照组(382.26±37.58，

0.05)和空载体对照组(365.48±32.68，

0.05)；AAV-proBDNF组海马PSD-95相对含量为(0.62±0.05)，明显低于正常对照组(0.82±0.02，

0.05)和空载体对照组(0.86±0.07，

0.05)。

结论

侧脑室注射AAV-proBDNF能够在AD鼠脑内成功表达proBDNF，并可降低AD鼠海马区新生神经元数量及突触可塑性。

Abstract

Objective

To explore the effects of lateral ventricle injection of recombinant adeno-associated virus-brain-derived neurotrophic factor precursor (AAV-proBDNF) on the hippocampal neurogenesis in APPswePS1dE9 transgenic mice (Alzheimer's disease

AD).

Methods

Fifteen APP/PS1 dE9 transgenic mice (5 months old) were randomly divided into normal control

empty vector control and AAV-proBDNF groups (

=5 in each group). Recombinant vectors of AAV-proBDNF (8×10

v.g.) were stereotaxically delivered into the right lateral ventricle in the AAV-proBDNF group

and empty AAV vector and normal saline (4 μL) were given respectively to the mice from the empty vector control and normal control groups. Enzyme-linked imm

unosorbent assay was conducted to test the proBDNF level in the brain in 4 weeks after injection. The count of doublecortin (DCX) positive cells and the expression of postsynaptic density-95 (PSD-95) in the hippocampus were detected by immunohistochemical assay and Western blotting respectively.

Results

In 4 weeks after injection

the proBDNF level was significantly higher in the AAV-proBDNF group than the normal control group and the empty vector control group (

0.05). The number of DCX-positive cells in the hippocampus of AAV-proBDNF group (202.46±24.27) was significantly lower than that in the normal control group (382.26±37.58

0.05) and empty vector control group (365.48±32.68

0.05). In AAV-proBDNF group

the relative content of PSD-95 (0.62±0.05) was obviously lower than the normal control group (0.82±0.02

0.05) and vector control group (0.86±0.07

0.05).

Conclusion

Lateral ventricle injection of AAV-proBDNF can induce the expression of proBDNF in the brain of AD mice

and reduce the number of new neurons and synaptic plasticity in the hippocampus.

关键词

Keywords

references

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