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脆性X综合征嵌合小鼠模型中人类特异性层间星形胶质细胞的活性

Activity of Human-Specific Interlaminar Astrocytes in a Chimeric Mouse Model of Fragile X Syndrome.

作者信息

Anding Alexandria, Ren Baiyan, Padmashri Ragunathan, Burkovetskaya Maria, Dunaevsky Anna

机构信息

Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.

出版信息

Int J Mol Sci. 2025 Jul 6;26(13):6510. doi: 10.3390/ijms26136510.

Abstract

Astrocytes, a subtype of glial cells, have multiple roles in regulating neuronal development and homeostasis. In addition to the typical mammalian astrocytes, in the primate cortex, interlaminar astrocytes are located in the superficial layer and project long processes traversing multiple layers of the cerebral cortex. Previously, we described a human stem cell based chimeric mouse model where interlaminar astrocytes develop. Here, we utilized this model to study the calcium signaling properties of interlaminar astrocytes. To determine how interlaminar astrocytes could contribute to neurodevelopmental disorders, we generated a chimeric mouse model for Fragile X syndrome (FXS). We report that FXS interlaminar astrocytes exhibit hyperexcitable calcium signaling and are associated with dendritic spines with increased turnover rate.

摘要

星形胶质细胞是神经胶质细胞的一种亚型,在调节神经元发育和内环境稳态方面具有多种作用。除了典型的哺乳动物星形胶质细胞外,在灵长类动物的皮质中,层间星形胶质细胞位于表层,并伸出长突起穿过大脑皮质的多层结构。此前,我们描述了一种基于人类干细胞的嵌合小鼠模型,层间星形胶质细胞在该模型中发育。在此,我们利用该模型研究层间星形胶质细胞的钙信号特性。为了确定层间星形胶质细胞如何导致神经发育障碍,我们构建了脆性X综合征(FXS)的嵌合小鼠模型。我们报告称,FXS层间星形胶质细胞表现出过度兴奋的钙信号,并且与周转率增加的树突棘相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72a5/12250119/6b96d33328b9/ijms-26-06510-g001.jpg

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