Loss of liver X receptor β in astrocytes leads to defects in early postnatal hippocampal neurogenesis in mice

Keyi LYU; Yi LUO; Xin LI; Rui XIAO; Sheng CHEN; Ruxin XIE; Xiaotang FAN; Hong CHEN

doi:10.16016/j.2097-0927.202110115

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Loss of liver X receptor β in astrocytes leads to defects in early postnatal hippocampal neurogenesis in mice

Basic Medicine | 更新时间：2026-01-09

- Loss of liver X receptor β in astrocytes leads to defects in early postnatal hippocampal neurogenesis in mice
- Journal of Army Medical University Vol. 44, Issue 5, Pages: 448-454(2022)
- 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：
- 基金信息：
- DOI：10.16016/j.2097-0927.202110115
  CLC： R-332;R321.6;R322.81
- Received：20 October 2021，
  
  Revised：2021-11-22，
  
  Published：15 March 2022
- 稿件说明：
移动端阅览
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：

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

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

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

，

=3)和星形胶质细胞中特异性LXRβ敲除组(LXRβ cKO

GFAP

，

=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

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(

0.05)、海马颗粒层SOX2标记的神经前体细胞数(

0.01)、SOX2/GFAP共同标记的放射状胶质细胞数(

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(

0.05)，Prox1的表达差异无统计学意义。

结论

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

To investigate the effects of specific liver X receptor β (LXRβ) knockout in astrocytes on early postnatal hippocampal neurogenesis in mice.

Methods

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

=3) and astrocyte specific LXRβ knockout group (LXRβ cKO

GFAP

=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

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 (

0.05)

while less numbers of Sox2-labeled neural precursor cells (

0.01) and SOX2/GFAP co-labeled radial glial cells (RGCs) (

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 (

0.05)

whilse the level of Prox1 between the 2 groups was not significant.

Conclusion

Specific knockout of LXRβ in astrocytes inhibits early postnatal neurogenesis of hippocampal DG in mice.

关键词

Keywords

references

LEUSSINK S, ARANDA-PARDOS I, A-GONZALEZ N. Lipid metabolism as a mechanism of immunomodulation in macrophages: the role of liver X receptors[J]. Curr Opin Pharmacol, 2020, 53: 18-26. DOI: 10.1016/j.coph.2020.02.003.

WANG B, TONTONOZ P. Liver X receptors in lipid signalling and membrane homeostasis[J]. Nat Rev Endocrinol, 2018, 14(8): 452-463. DOI: 10.1038/s41574-018-0037-x.

LINDSEY B W, HALL Z J, HEUZÉ A, et al . The role of neuro-epithelial-like and radial-glial stem and progenitor cells in development, plasticity, and repair[J ] . Prog Neurobiol, 2018, 170: 99-114. DOI: 10.1016/j.pneurobio.2018.06.004.

KYROUSI C, LYGEROU Z, TARAVIRAS S. How a radial glial cell decides to become a multiciliated ependymal cell[J]. Glia, 2017, 65(7): 1032-1042. DOI: 10.1002/glia.23118.

CAI Y L, TANG X T, CHEN X, et al . Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse[J ] . Proc Natl Acad Sci U SA, 2018, 115(12): E2725-E2733. DOI: 10.1073/pnas.1800184115.

SUN T, LI Y J, TIAN Q Q, et al . Activation of liver X receptor β-enhancing neurogenesis ameliorates cognitive impairment induced by chronic cerebral hypoperfusion[J ] . Exp Neurol, 2018, 304: 21-29. DOI: 10.1016/j.expneurol.2018.02.006.

BABURAMANI A A, VONTELL R T, UUS A, et al . Assessment of radial glia in the frontal lobe of fetuses with Down syndrome[J ] . Acta Neuropathol Commun, 2020, 8(1): 141. DOI: 10.1186/s40478-020-01015-3.

MARTÍ-CLÚA J. Incorporation of 5-bromo-2'-deoxyuridine into DNA and proliferative behavior of cerebellar neuroblasts: all that glitters is not gold[J]. Cells, 2021, 10(6): 1453. DOI: 10.3390/cells10061453.

MERCURIO S, SERRA L, NICOLIS S K. More than just stem cells: functional roles of the transcription factor Sox2 in differentiated Glia and neurons[J]. Int J Mol Sci, 2019, 20(18): E4540. DOI: 10.3390/ijms20184540.

OCHI S, SEKIYA K, ABE N, et al . Neural precursor cells are decreased in the Hippocampus of the delayed carbon monoxide encephalopathy rat model[J ] . Sci Rep, 2021, 11(1): 6244 . DOI: 10.1038/s41598-021-85860-9.

JOHNSON K, BARRAGAN J, BASHIRUDDIN S, et al . Gfap-positive radial glial cells are an essential progenitor population for later-born neurons and glia in the zebrafish spinal cord[J ] . Glia, 2016, 64(7): 1170-1189. DOI: 10.1002/glia.22990.

LI G N, PLEASURE S J. Morphogenesis of the dentate gyrus: what we are learning from mouse mutants[J]. Dev Neurosci, 2005, 27(2/3/4): 93-99. DOI: 10.1159/000085980.

ROQUE A, LAJUD N, VALDEZ J J, et al . Early-life stress increases granule cell density in the cerebellum of male rats[J ] . Brain Res, 2019, 1723: 146358. DOI: 10.1016/j.brainres.2019.146358.

KEMPERMANN G, SONG H, GAGE F H. Neurogenesis in the adult hippocampus[J]. Cold Spring Harb Perspect Biol, 2015, 7(9): a018812. DOI: 10.1101/cshperspect.a018812.

XU L, TANG X, WANG Y, et al . Radial glia, the keystone of the development of the hippocampal dentate gyrus[J ] . Mol Neurobiol, 2015, 51(1): 131-141. DOI: 10.1007/s12035-014-8692-y.

DE JUAN ROMERO C, BORRELL V. Coevolution of radial glial cells and the cerebral cortex[J]. Glia, 2015, 63(8): 1303-1319. DOI: 10.1002/glia.22827.

BERG D A, BOND A M, MING G L, et al . Radial glial cells in the adult dentate gyrus: what are they and where do they come from?[J ] . F1000Res, 2018, 7: 277. DOI: 10.12688/f1000research.12684.1.

ALLEN N J, LYONS D A. Glia as architects of central nervous system formation and function[J]. Science, 2018, 362(6411): 181-185. DOI: 10.1126/science.aat0473.

KAWAGUCHI A. Neuronal delamination and outer radial Glia generation in neocortical development[J]. Front Cell Dev Biol, 2020, 8: 623573. DOI: 10.3389/fcell.2020.623573.

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