Calcitonin gene-related peptide (CGRP) triggers Ca2+ responses in cultured astrocytes and in Bergmann glial cells from cerebellar slices.

Calcitonin gene-related peptide (CGRP) triggers Ca2+ responses in cultured astrocytes and in Bergmann glial cells from cerebellar slices.
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DOI:
10.1111/j.1460-9568.2008.06514.x
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发表时间:
2008-12
期刊:
The European journal of neuroscience
影响因子:
--
通讯作者:
Kettenmann H
Kettenmann H
中科院分区:
其他
文献类型:
--
作者:
Morara S;Wang LP;Filippov V;Dickerson IM;Grohovaz F;Provini L;Kettenmann H

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神经肽降钙素基因相关肽(CGRP)在发育过程中在小脑攀爬纤维中瞬时表达,而其受体主要在星形胶质细胞,特别是Bergmann胶质细胞中表达。在这里,我们分析了CGRP对星形胶质细胞钙信号的影响。将来自小脑或大脑皮质的小鼠培养的星形胶质细胞以及来自急性分离的小脑切片的Bergmann神经胶质细胞加载有Ca 2+传感器Fura-2。CGRP触发短暂增加细胞内Ca 2+在星形胶质细胞培养以及在急性切片。在1 nM至1 mM的浓度范围内,在细胞体及其过程中均观察到响应。钙瞬变依赖于从细胞内存储的释放,因为它们被毒胡萝卜素阻断,但不存在细胞外钙。此外,在CGRP应用后,可以观察到钙活性的进一步延迟的瞬时增加。最后,从新生小鼠小脑星形胶质细胞表达受体组分蛋白,CGRP受体的一个组成部分,如免疫荧光和共聚焦显微镜所示。因此,建议在小脑中含有CGRP的传入纤维(攀爬纤维)调节星形胶质细胞中的钙通过释放神经肽在发育过程中,因此可能影响浦肯野细胞的分化。
The neuropeptide calcitonin gene-related peptide (CGRP) is transiently expressed in cerebellar climbing fibers during development while its receptor is mainly expressed in astrocytes, in particular Bergmann glial cells. Here, we analyzed the effects of CGRP on astrocytic calcium signaling. Mouse cultured astrocytes from cerebellar or cerebral cortex as well as Bergmann glial cells from acutely isolated cerebellar slices were loaded with the Ca2+ sensor Fura-2. CGRP triggered transient increases in intracellular Ca2+ in astrocytes in culture as well as in acute slices. Responses were observed in the concentration range of 1 nM to 1 mM, in both the cell body and its processes. The calcium transients were dependent on release from intracellular stores as they were blocked by thapsigargin but not by the absence of extracellular calcium. In addition, after CGRP application a further delayed transient increase in calcium activity could be observed. Finally, cerebellar astrocytes from neonatal mice expressed receptor component protein, a component of the CGRP receptor, as revealed by immunofluorescence and confocal microscopy. It is thus proposed that the CGRP-containing afferent fibers in the cerebellum (the climbing fibers) modulate calcium in astrocytes by releasing the neuropeptide during development and hence possibly influence the differentiation of Purkinje cells.
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