Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin<sup>+</sup> dendritic spines in different hippocampal subregions of mice

Shun WANG; Lin JIANG; Qi HE; Hao YANG; Yiying WANG; Yuning ZHOU; Xin LIANG; Yi ZHANG; Fenglei CHAO; Lei ZHANG; Yong TANG

doi:10.16016/j.2097-0927.202306100

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Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin⁺ dendritic spines in different hippocampal subregions of mice

Basic Medicine | 更新时间：2026-01-09

- Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin⁺ dendritic spines in different hippocampal subregions of mice
- Journal of Army Medical University Vol. 46, Issue 2, Pages: 118-127(2024)
- 作者机构：
  
  400016 重庆，重庆医科大学基础医学院组织学与胚胎学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82002227);the General Program of Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0105);the General Program of Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0354)
- DOI：10.16016/j.2097-0927.202306100
  CLC： R338.26;R338.64;R394.3
- Received：26 June 2023，
  
  Revised：2023-08-04，
  
  Published：30 January 2024
- 稿件说明：
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Shun WANG, Lin JIANG, Qi HE, et al. Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin⁺ dendritic spines in different hippocampal subregions of mice[J]. Journal of Army Medical University, 2024, 46(2): 118-127.
DOI：

Shun WANG, Lin JIANG, Qi HE, et al. Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin⁺ dendritic spines in different hippocampal subregions of mice[J]. Journal of Army Medical University, 2024, 46(2): 118-127. DOI： 10.16016/j.2097-0927.202306100.

摘要

目的

脑立体定位注射腺相关病毒特异性过表达海马LINGO-1，探讨其对小鼠空间学习和记忆能力以及海马各亚区体积和Spinophilin

树突棘的影响。

方法

将7月龄雄性C57小鼠按照简单随机法分为对照组和LINGO-1过表达组，对照组小鼠海马立体定位注射携带绿色荧光的空载腺相关病毒(adeno-associated virus，AAV)，LINGO-1过表达组小鼠海马立体定位注射同时携带绿色荧光和LINGO-1过表达载体的AAV。运用Morris水迷宫评估小鼠的空间学习和记忆能力，荧光定量PCR及免疫荧光染色方法分别检测小鼠海马内LINGO-1基因表达水平和各亚区荧光强度，体视学三维定量小鼠海马各亚区体积及Spinophilin

树突棘总数。

结果

对照组和LINGO-1过表达组病毒注射前后体质量差异无统计学意义；LINGO-1过表达诱导小鼠海马LINGO-1的mRNA水平升高、荧光强度增强(

0.01)；与对照组相比，LINGO-1过表达组

小鼠在Morris水迷宫实验中的表现明显更差(

0.05)；LINGO-1过表达诱导小鼠海马各亚区体积显著下降(

0.05

0.01)，Spinophilin

树突棘密度显著降低(

0.01

0.05)，Spinophilin

树突棘数量显著减少(

0.05)。

结论

海马立体定位注射过表达LINGO-1腺相关病毒能够特异性上调小鼠海马内LINGO-1水平，海马LINGO-1的异常高表达可导致小鼠海马体积减小及Spinophilin

树突棘突触丢失，并在一定程度上损伤其空间学习与记忆能力。

Abstract

Objective

To investigate the effects of adenovirus-associated virus (AAV)-mediated overexpression of LINGO-1 in the hippocampus on spatial learning and memory abilities

as well as the volume and Spinophilin

dendritic spines of different subregions within the hippocampus in mice.

Methods

Male C57 mice at 7 months of age were randomly divided into a control group and a LINGO-1 overexpression group. The control group received hippocampal stereotaxic injection of AAV carrying green fluorescent protein (GFP)

while the LINGO-1 overexpression group received hippocampal stereotaxic injection of AAV carrying both GFP and LINGO-1 overexpression vector. Morris water maze was used to evaluate spatial learning and memory abilities of the mice. Quantitative PCR and immunofluorescence staining were used to detect LINGO-1 mRNA expression and fluorescence intensity in the hippocampus

and 3-dimensional stereology was used to quantify the volume and the total number of Spinophilin

dendritic spines.

Results

There was no significant difference in body weight between the control group and the LINGO-1 overexpression group before and after virus injection. LINGO-1 overexpression induced an increase in hippocampal LINGO-1 at mRNA level and in fluorescent intensity(

0.01). The LINGO-1 overexpression group performed significantly worse in the Morris water maze test compared t

o the control group(

0.05). Moreover

LINGO-1 overexpression led to a significant reduction in the volumes of different hippocampal subregions(

0.05

0.01)

accompanied by marked decreases in the density(

0.01

0.05) and total number of Spinophilin

dendritic spines(

0.05).

Conclusion

Stereotaxic injection of AAV-mediated LINGO-1 overexpression specifically upregulates LINGO-1 in the hippocampus of mice. Abnormally high expression of LINGO-1 in the hippocampus leads to decreased hippocampal volume and loss of Spinophilin

dendritic spines

as well as impaires spatial learning and memory abilities of mice to a certain extent.

关键词

Keywords

references

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⁰

Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin+ dendritic spines in different hippocampal subregions of mice

DOI：10.16016/j.2097-0927.202306100

摘要

Abstract

关键词

Keywords

references

Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin⁺ dendritic spines in different hippocampal subregions of mice