Pituitary Adenylate Cyclase-Activating Polypeptide Induces Astrocyte Differentiation of Precursor Cells from Developing Cerebral Cortex
Pituitary Adenylate Cyclase-Activating Polypeptide Induces Astrocyte Differentiation of Precursor Cells from Developing Cerebral Cortex
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DOI：
10.1006/mcne.2002.1189
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发表时间：
2002-12
影响因子：
3.5
通讯作者：
I. Vallejo;M. Vallejo
中科院分区：
文献类型：
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作者：
I. Vallejo;M. Vallejo
纤毛神经营养因子和骨形态发生蛋白分别通过刺激STAT和smad依赖的信号传导诱导发育中的大鼠脑中的星形细胞发生。我们之前发现，刺激camp依赖的信号通路也会触发大脑皮层前体细胞向星形胶质细胞的分化，这为促进星形胶质细胞分化提供了另一种机制。在这项研究中，我们发现垂体腺苷酸环化酶激活多肽（PACAP），而不是相关的血管活性肠肽，诱导皮质前体细胞的星形胶质细胞分化，即使在短暂暴露后也是如此。发现皮质前体主要表达pacap特异性PAC1受体的短异构体，该受体与腺苷酸环化酶偶联。与这一观点一致，我们确定皮质前体暴露于PACAP导致cAMP产量的剂量依赖性增加。用cAMP拮抗剂rp -cAMP预处理细胞可阻止星形胶质细胞分化。因此，PACAP作为细胞外信号，通过刺激细胞内cAMP的产生，触发皮层前体细胞分化为星形胶质细胞。
Ciliary neurotrophic factor and bone morphogenetic proteins induce astrocytogenesis in the developing rat brain by stimulating STAT- and Smad-dependent signaling, respectively. We previously found that stimulation of the cAMP-dependent signaling pathway also triggers differentiation of cerebral cortical precursor cells into astrocytes, providing an additional mechanism to promote astrocyte differentiation. In this study, we show that pituitary adenylate cyclase-activating polypeptide (PACAP), but not the related vasoactive intestinal peptide, induces astrocyte differentiation of cortical precursor cells, even after a transient exposure. Cortical precursors were found to express predominantly the short isoform of the PACAP-specific PAC1 receptor, which couples to adenylate cyclase. Consistent with this notion, we determined that exposure of cortical precursors to PACAP resulted in a dose-dependent increase in cAMP production. Pretreatment of cells with the cAMP antagonist Rp-cAMPS prevented astrocyte differentiation. Thus, PACAP acts as an extracellular signal to trigger cortical precursor cell differentiation into astrocytes via stimulation of intracellular cAMP production.