Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
School of Physics and Astronomy, Tel Aviv University, 69978 Tel Aviv, Israel.
Proc Natl Acad Sci U S A. 2018 Jul 31;115(31):8025-8030. doi: 10.1073/pnas.1718582115. Epub 2018 Jul 16.
Evidence suggests that astrocytes play key roles in structural and functional organization of neuronal circuits. To understand how astrocytes influence the physiopathology of cerebellar circuits, we cultured cells from cerebella of mice that lack the gene. Mutations in are causative of the human cerebellar degenerative disease ataxia-telangiectasia. Cerebellar cultures grown from mice had disrupted network synchronization, atrophied astrocytic arborizations, reduced autophagy levels, and higher numbers of synapses per neuron than wild-type cultures. Chimeric circuitries composed of wild-type astrocytes and neurons were indistinguishable from wild-type cultures. Adult cerebellar characterizations confirmed disrupted astrocyte morphology, increased GABAergic synaptic markers, and reduced autophagy in compared with wild-type mice. These results indicate that astrocytes can impact neuronal circuits at levels ranging from synaptic expression to global dynamics.
有证据表明，星形胶质细胞在神经元回路的结构和功能组织中发挥着关键作用。为了了解星形胶质细胞如何影响小脑回路的病理生理学，我们培养了缺乏 基因的小鼠小脑细胞。 在人类小脑退行性疾病共济失调-毛细血管扩张症中， 基因的突变是致病原因。与野生型培养物相比，源自 基因敲除小鼠的小脑培养物表现出网络同步中断、星形胶质细胞树突分支萎缩、自噬水平降低以及每个神经元的突触数量增加。由野生型星形胶质细胞和 神经元组成的嵌合电路与野生型培养物没有区别。成年小脑特征证实，与野生型小鼠相比， 小鼠的星形胶质细胞形态破坏、GABA 能突触标志物增加和自噬减少。这些结果表明，星形胶质细胞可以在从突触表达到全局动力学的各个层面上影响神经元回路。
