Abnormal social behavior and altered gene expression in mice lacking NDRG2
Abnormal social behavior and altered gene expression in mice lacking NDRG2
复制标题
DOI：
10.1016/j.neulet.2020.135563
复制
发表时间：
2020-12
影响因子：
2.5
通讯作者：
Mika Takarada-Iemata;T. Yoshihara;Nahoko Okitani;Keiko Iwata;T. Hattori;H. Ishii;J. Roboon;D. T. Nguy
中科院分区：
文献类型：
--
作者：
Mika Takarada-Iemata;T. Yoshihara;Nahoko Okitani;Keiko Iwata;T. Hattori;H. Ishii;J. Roboon;D. T. Nguy
N-myc下游调控基因2 （NDRG2）是NDRG家族的成员，在细胞增殖、分化和应激反应中具有多种功能，主要在中枢神经系统星形胶质细胞中表达。包括我们在内的先前研究表明，NDRG2参与了各种中枢神经系统病理。然而，NDRG2在神经发育中的意义尚不完全清楚。在这里，我们研究了NDRG2在出生后大脑发育过程中的表达谱，NDRG2在社会行为中的作用，以及NDRG2缺陷小鼠大脑中的转录组变化。大脑中NDRG2的表达从出生后第一天到成年后随着时间的推移而增加。NDRG2的缺失导致了异常的社会行为，在三室社会互动测试中，对一种新型小鼠的探索活动减少表明了这一点。微阵列分析鉴定了ndrg2缺陷脑中差异表达的基因，定量PCR分析证实了bmp4和per2基因表达上调。在出生后的大脑发育过程中，这些基因和编码蛋白的表达随着时间的推移而增加，与NDRG2相似。从ndrg2缺失小鼠分离的培养星形胶质细胞中，bmp4和per2基因表达上调。这些结果表明，NDRG2通过调节星形胶质细胞中的基因表达，促进了大脑发育所需的适当社会行为。
N-myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family, has multiple functions in cell proliferation, differentiation, and stress responses, and is predominantly expressed by astrocytes in the central nervous system. Previous studies including ours demonstrated that NDRG2 is involved in various central nervous system pathologies. However, the significance of NDRG2 in neurodevelopment is not fully understood. Here, we investigated the expression profile of NDRG2 during postnatal brain development, the role of NDRG2 in social behavior, and transcriptome changes in the brain of NDRG2-deficient mice. NDRG2 expression in the brain increased over time from postnatal day 1 to adulthood. Deletion of NDRG2 resulted in abnormal social behavior, as indicated by reduced exploratory activity toward a novel mouse in a three-chamber social interaction test. Microarray analysis identified genes differentially expressed in the NDRG2-deficient brain, and upregulated gene expression ofBmp4andPer2was confirmed by quantitative PCR analysis. Expression of both these genes and the encoded proteins increased over time during postnatal brain development, similar to NDRG2. Gene expression ofBmp4andPer2was upregulated in cultured astrocytes isolated from NDRG2-deficient mice. These results suggest that NDRG2 contributes to brain development required for proper social behavior by modulating gene expression in astrocytes.