Priller J, Haas C A, Reddington M, Kreutzberg G W
Department of Neuromorphology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Glia. 1998 Nov;24(3):323-8. doi: 10.1002/(sici)1098-1136(199811)24:3<323::aid-glia6>3.0.co;2-2.
The neuropeptides galanin and calcitonin gene-related peptide (CGRP) are strongly up-regulated in motoneurons following axotomy. Earlier reports have suggested that peptides might be released from injured neurons to recruit surrounding glia. In this study, the effects of galanin and CGRP on cultured rat astrocytes were investigated using the expression of immediate early genes as a model for receptor-mediated transcriptional activation. Galanin was found to induce c-fos, junB, and Tis11 mRNA in cultured astrocytes, providing evidence for the presence of functional galanin receptors on neuroglial cells. In contrast, CGRP only led to the induction of c-fos and junB mRNA. Cholecystokinin (CCK-8) and substance P, which are also up-regulated in select motoneuron populations following axotomy, fail to induce immediate early genes in astrocytes, indicating specificity of neuropeptides in their ability to stimulate glial cells. The differential induction of immediate early gene expression by galanin and CGRP in astrocytes points to differences in intracellular signal transduction mechanisms. Whereas CGRP was found to stimulate the accumulation of cyclic AMP by 10- to 20-fold, galanin had no effect on basal cyclic AMP content. The effect of CGRP on cyclic AMP accumulation was completely reversed by the CGRP receptor antagonist, CGRP(8-37). These results suggest roles for galanin and CGRP in the transcriptional activation of astrocytes.
神经肽甘丙肽和降钙素基因相关肽(CGRP)在轴突切断后的运动神经元中强烈上调。早期报告表明,肽可能从受损神经元释放以募集周围的神经胶质细胞。在本研究中,以即刻早期基因的表达作为受体介导的转录激活模型,研究了甘丙肽和CGRP对培养的大鼠星形胶质细胞的影响。发现甘丙肽可诱导培养的星形胶质细胞中c-fos、junB和Tis11 mRNA的表达,为神经胶质细胞上存在功能性甘丙肽受体提供了证据。相比之下,CGRP仅导致c-fos和junB mRNA的诱导。胆囊收缩素(CCK-8)和P物质在轴突切断后的特定运动神经元群体中也上调,但它们不能诱导星形胶质细胞中的即刻早期基因,表明神经肽在刺激神经胶质细胞的能力方面具有特异性。甘丙肽和CGRP在星形胶质细胞中对即刻早期基因表达的差异诱导表明细胞内信号转导机制存在差异。虽然发现CGRP可使环磷酸腺苷(cAMP)的积累增加10至20倍,但甘丙肽对基础cAMP含量没有影响。CGRP受体拮抗剂CGRP(8-37)可完全逆转CGRP对cAMP积累的作用。这些结果表明甘丙肽和CGRP在星形胶质细胞的转录激活中发挥作用。