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 receptorβin astrocytes leads to defects in early postnatal hippocampal neurogenesis in mice

作　　者：吕柯毅 骆燚 李欣[2] 肖锐[2] 陈胜 谢汝欣 范晓棠[2] 陈红 LYU Keyi;LUO Yi;LI Xin;XIAO Rui;CHEN Sheng;XIE Ruxin;FAN Xiaotang;CHEN Hong(Key Laboratory of Cognition and Personality of Ministry of Education,Faculty of Psychology,Southwest University,Chongqing,400715;Department of Military Cognitive Psychology,Faculty of Medical Psychology,Army Medical University(Third Military Medical University),Chongqing,400038,China)

机构地区：[1]西南大学心理学部,认知与人格教育部重点实验室,重庆400715 [2]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,重庆400038

出　　处：《陆军军医大学学报》2022年第5期448-454,共7页Journal of Army Medical University

基　　金：国家自然科学基金面上项目(82071544)。

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),n=3)和星形胶质细胞中特异性LXRβ敲除组(LXRβcKO^(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HE染色结果显示,P2、P7时,与LXRβ^(fl/fl)组相比,LXRβcKO^(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,LXRβcKO^(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,LXRβcKO^(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。ObjectiveTo investigate the effects of specific liver X receptorβ(LXRβ)knockout in astrocytes on early postnatal hippocampal neurogenesis in mice.MethodsCre/loxP system was used to construct a mouse model with specific LXRβknockout in astrocyte.Then the mice were divided into control group(LXRβ^(fl/fl),n=3)and astrocyte specific LXRβknockout group(LXRβcKO^(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.ResultsHE staining showed no great changes in the structure and area of hippocampal DG between the LXRβ^(fl/fl) and LXRβcKO^(GFAP) groups at P2 and P7.For the P7 mice,the LXRβcKO^(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 LXRβcKO^(GFAP) mice was remarkably reduced(P<0.05),whilse the level of Prox1 between the 2 groups was not significant.ConclusionSpecific knockout of LXRβin astrocytes inhibits early postnatal neurogenesis of hippocampal DG in mice.

关 键 词：肝X受体 海马 神经发生 星形胶质细胞 

分 类 号：R-332[医药卫生] R321.6