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Publishing Language: Chinese

Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin+ 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()
Department of Histology and Embryology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China
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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(P < 0.01). The LINGO-1 overexpression group performed significantly worse in the Morris water maze test compared to the control group(P < 0.05). Moreover, LINGO-1 overexpression led to a significant reduction in the volumes of different hippocampal subregions(P < 0.05, P < 0.01), accompanied by marked decreases in the density(P < 0.01, P < 0.05) and total number of Spinophilin+ dendritic spines(P < 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.

Keywords

LINGO-1dendritic spinesynapseshippocampuslearningmemory
CLC number: R338.26;R338.64;R394.3 Document code: A

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Journal of Army Medical University
Volume 46 Issue 2,
January 2024
Pages 118-127
DOI: 10.16016/j.2097-0927.202306100
Cite this article:
WANG S, JIANG L, HE Q, et al. 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, 2024, 46(2): 118-127. https://doi.org/10.16016/j.2097-0927.202306100
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