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星形胶质细胞中LXRβ缺失对生后早期海马神经发生的影响
Loss of liver X receptor β in astrocytes leads to defects in early postnatal hippocampal neurogenesis in mice
- 陆军军医大学学报 2022年44卷第5期 页码：448-454
- 作者机构：
1.400715 重庆，西南大学心理学部，认知与人格教育部重点实验室
2.400038 重庆，陆军军医大学(第三军医大学)医学心理系军事认知心理学教研室
- 作者简介：
[ 范晓棠，E-mail：fanxiaotang2005@163.com FAN Xiaotang, E-mail: fanxiaotang2005@163.com
[ 陈红，E-mail：chenhg@swu.edu.cn CHEN Hong, E-mail: chenhg@swu.edu.cn
- 基金信息：the General Program of Natural Science Foundation of China(82071544)
DOI：10.16016/j.2097-0927.202110115
中图分类号： R-332;R321.6;R322.81收稿：2021-10-20，
修回：2021-11-22，
纸质出版：2022-03-15
- 稿件说明：
移动端阅览
吕柯毅, 骆邁, 李欣, 等. 星形胶质细胞中LXRβ缺失对生后早期海马神经发生的影响[J]. 陆军军医大学学报, 2022,44(5):448-454.
Keyi LYU, Yi LUO, Xin LI, et al. Loss of liver X receptor β in astrocytes leads to defects in early postnatal hippocampal neurogenesis in mice[J]. Journal of Army Medical University, 2022, 44(5): 448-454.
吕柯毅, 骆邁, 李欣, 等. 星形胶质细胞中LXRβ缺失对生后早期海马神经发生的影响[J]. 陆军军医大学学报, 2022,44(5):448-454. DOI： 10.16016/j.2097-0927.202110115.
Keyi LYU, Yi LUO, Xin LI, et al. Loss of liver X receptor β in astrocytes leads to defects in early postnatal hippocampal neurogenesis in mice[J]. Journal of Army Medical University, 2022, 44(5): 448-454. DOI： 10.16016/j.2097-0927.202110115.
摘要
目的
2
研究星形胶质细胞中特异性敲除LXRβ对生后早期海马神经发生的影响。
方法
2
使用Cre/LoxP系统构建星形胶质细胞中特异性LXRβ敲除小鼠。实验分为：对照组(LXRβ
fl/fl
，
n
=3)和星形胶质细胞中特异性LXRβ敲除组(LXRβ cKO
GFAP
，
n
=3)。生后7 d(postnatal day 7，P7)，小鼠予以5-溴脱氧尿嘧啶核苷(5-bromo-2’-deoxyuridine，BrdU)腹腔注射，给药后2 h收取P7脑标本，HE染色观察小鼠P2和P7脑标本海马结构的变化，免疫荧光染色检测P7时小鼠海马齿状回BrdU、SOX2/GFAP、NeuN和Prox1表达，以及P14时小鼠海马齿状回NeuN和Prox1表达。
结果
2
HE染色结果显示，P2、P7时，与LXRβ
fl/fl
组相比，LXRβ cKO
GFAP
组小鼠海马齿状回的大体结构无明显改变，两组间海马齿状回面积差异无统计学意义；在P7时
与LXRβ
fl/fl
组相比，LXRβ cKO
GFAP
组小鼠海马齿状回门区BrdU阳性细胞数量显著增多(
P
<
0.05)、海马颗粒层SOX2标记的神经前体细胞数(
P
<
0.01)、SOX2/GFAP共同标记的放射状胶质细胞数(
P
<
0.05)显著减少，未成熟神经元标志物Prox1和成熟神经元标志物NeuN在两组中的表达均无统计学差异。在P14时，与LXRβ
fl/fl
组相比，LXRβ cKO
GFAP
组小鼠海马齿状回NeuN的表达显著减少(
P
<
0.05)，Prox1的表达差异无统计学意义。
结论
2
特异性敲除小鼠星形胶质细胞中LXRβ抑制生后早期海马齿状回神经发生。
Abstract
Objective
2
To investigate the effects of specific liver X receptor β (LXRβ) knockout in astrocytes on early postnatal hippocampal neurogenesis in mice.
Methods
2
Cre/loxP system was used to construct a mouse model
with specific LXRβ knockout in astrocyte. Then the mice were divided into control group (LXRβ
fl/fl
n
=3) and astrocyte specific LXRβ knockout group (LXRβ cKO
GFAP
n
=3). On postnatal day 7 (P7)
both groups were intraperitoneally injected with 5-Bromo-2'-deoxyuridine (BrdU)
and the brain samples of mice were collected 2 h after drug administration. HE staining was performed on brain samples of the P2 and P7 mice to compare the changes of hippocampal structure between the 2 groups. The expression levels of BrdU
SOX2/GFAP
NeuN and Prox1 in the hippocampal dentate gyrus (DG) were detected in the P7 mice by immunofluorescence staining
so as the levels of NeuN and Prox1 in the P14 mice.
Results
2
HE staining showed no great changes in the structure and area of hippocampal DG between the LXRβ
fl/fl
and LXRβ cKO
GFAP
groups at P2 and P7. For the P7 mice
the LXRβ cKO
GFAP
group had larger number of BrdU-labeled positive cells in DG of the hippocampus (
P
<
0.05)
while less numbers of Sox2-labeled neural precursor cells (
P
<
0.01) and SOX2/GFAP co-labeled radial glial cells (RGCs) (
P
<
0.05) in DG layer as compared with the LXRβ
fl/fl
group. There was no statistical significance in the expression of immature neuron marker Prox1 and mature neuron marker NeuN between the 2 groups. At P14
the expression of NeuN in the DG of LXRβ cKO
GFAP
mice was remarkably reduced (
P
<
0.05)
whilse the level of Prox1 between the 2 groups was not significant.
Conclusion
2
Specific knockout of LXRβ in astrocytes inhibits early postnatal neurogenesis of hippocampal DG in mice.
关键词
Keywords
references
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