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

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 (LXRβfl/fl, n=3) and astrocyte specific LXRβ knockout group (LXRβ cKOGFAP, 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 HE staining showed no great changes in the structure and area of hippocampal DG between the LXRβfl/fl and LXRβ cKOGFAP groups at P2 and P7. For the P7 mice, the LXRβ cKOGFAP 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 LXRβfl/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 cKOGFAP mice was remarkably reduced (P < 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.

Keywords

• liver x receptor
• hippocampus
• neurogenesis
• astrocytes