[1]许曼玉,陈甲,许志强.AAV-proBDNF对阿尔茨海默病鼠海马DCX阳性细胞数及PSD-95表达的影响[J].第三军医大学学报,2019,41(02):95-99.
 XU Manyu,CHEN Jia,XU Zhiqiang.Effects of AAV-proBDNF on hippocampal DCX positive cells and PSD-95 expression in Alzheimer’s disease mice[J].J Third Mil Med Univ,2019,41(02):95-99.
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AAV-proBDNF对阿尔茨海默病鼠海马DCX阳性细胞数及PSD-95表达的影响(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第02期
页码:
95-99
栏目:
基础医学
出版日期:
2019-01-30

文章信息/Info

Title:
Effects of AAV-proBDNF on hippocampal DCX positive cells and PSD-95 expression in Alzheimer’s disease mice
作者:
许曼玉陈甲许志强
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
Author(s):
XU Manyu CHEN Jia XU Zhiqiang

Department of Neurology, Institute of Surgery Research, Third Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China

关键词:
脑源性神经营养因子前体阿尔茨海默病突触后致密物-95
Keywords:
brain-derived neurotrophic factor precursor Alzheimer&rsquos disease postsynaptic density-95
分类号:
R338.26;R394.3;R745.7
文献标志码:
A
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(n=5)、空载体对照组(n=5)和AAV-proBDNF组(n=5),AAV-proBDNF组右侧侧脑室注射AAV-proBDNF(4 μL, 2×1013 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(P<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,P<0.05)和空载体对照组(365.48±32.68,P<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,P<0.05)和空载体对照组(0.86±0.07,P<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 (n=5 in each group). Recombinant vectors of AAV-proBDNF (8×1010 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 immunosorbent 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 (P<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, P<0.05) and empty vector control group (365.48±32.68, P<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, P<0.05) and vector control group (0.86±0.07, P<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.

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更新日期/Last Update: 2019-01-22