小柯机器人

美国索尔克生物研究所Nicola J. Allen研究团队发现在多种神经发育障碍 (ND)模型中，异常的星形胶质细胞蛋白分泌有助于改变神经元发育。2022年8月30日出版的《自然—神经科学》发表了这项成果。

他们开发了一个细胞培养系统，以了解星形胶质细胞蛋白分泌和基因表达在三种遗传性ND 小鼠模型（Rett、脆性X和唐氏综合征）中的变化。ND星形胶质细胞增加Igfbp2的释放Igfbp2是一种分泌的胰岛素样生长因子 (IGF) 抑制剂。IGF挽救了许多ND的神经元缺陷，他们发现阻断Igfbp2部分挽救了Rett综合征星形胶质细胞的抑制作用，这表明增加的星形胶质细胞Igfbp2有助于降低ND中的IGF信号传导。

他们发现增加的BMP信号是蛋白质分泌变化的上游，包括Igfbp2，并且阻断脆性X和Rett综合征星形胶质细胞中的BMP信号会逆转对神经突生长的抑制作用。这项工作提供了健康和 ND 模型中星形胶质细胞分泌蛋白的资源，并确定了干预各种ND的新靶点。

据介绍，星形胶质细胞对许多ND模型中的神经元发育产生负面影响。然而，它们是如何做到这一点的，以及机制是否在疾病之间共享，尚不清楚。

附：英文原文

Title: Aberrant astrocyte protein secretion contributes to altered neuronal development in multiple models of neurodevelopmental disorders

Author: Caldwell, Alison L. M., Sancho, Laura, Deng, James, Bosworth, Alexandra, Miglietta, Audrey, Diedrich, Jolene K., Shokhirev, Maxim N., Allen, Nicola J.

Issue&Volume: 2022-08-30

Abstract: Astrocytes negatively impact neuronal development in many models of neurodevelopmental disorders (NDs); however, how they do this, and if mechanisms are shared across disorders, is not known. In this study, we developed a cell culture system to ask how astrocyte protein secretion and gene expression change in three mouse models of genetic NDs (Rett, Fragile X and Down syndromes). ND astrocytes increase release of Igfbp2, a secreted inhibitor of insulin-like growth factor (IGF). IGF rescues neuronal deficits in many NDs, and we found that blocking Igfbp2 partially rescues inhibitory effects of Rett syndrome astrocytes, suggesting that increased astrocyte Igfbp2 contributes to decreased IGF signaling in NDs. We identified that increased BMP signaling is upstream of protein secretion changes, including Igfbp2, and blocking BMP signaling in Fragile X and Rett syndrome astrocytes reverses inhibitory effects on neurite outgrowth. This work provides a resource of astrocyte-secreted proteins in health and ND models and identifies novel targets for intervention in diverse NDs.

DOI: 10.1038/s41593-022-01150-1

Source: https://www.nature.com/articles/s41593-022-01150-1

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex