Astrocytes and microglia as potential targets for calcitonin gene related peptide in the central nervous system

1995 ◽  
Vol 73 (7) ◽  
pp. 1047-1049 ◽  
Author(s):  
Martin Reddington ◽  
Josef Priller ◽  
Julia Treichel ◽  
Carola Haas ◽  
George W. Kreutzberg

Injury of peripheral motoneurons leads to the activation of astrocytes and microglia in the vicinity of the damaged neurons in the central nervous system. It has been proposed that neuropeptides such as the calcitonin gene related peptide (CGRP), which show an increased expression in motoneurons following axotomy, play a role as signalling molecules mediating the interactions between the damaged neurons and surrounding glial cells. Evidence supporting this hypothesis is provided by in vitro investigations of the actions of neuropeptides on glial cells. CGRP induces activation of both astrocytes and microglia at the transcriptional level, as seen by the stimulation of mRNA for the immediate early gene, c-fos, in these cells in culture. In addition to its stimulation of immediate early gene expression, treatment of astrocyte cultures with CGRP stimulated release of the tissue plasminogen activator and led to the accumulation of mRNAs for tissue plasminogen activator and the plasminogen activator inhibitor 1. These components of the plasminogen activator system, which has been implicated in processes of tissue remodelling, are upregulated in astrocytes in the facial nucleus in vivo after facial nerve axotomy. The data suggest a role for CGRP as a mediator of glial cell activation following motoneuron injury.Key words: calcitonin gene related peptide, plasminogen activator, immediate early genes, astrocytes, microglia.

1995 ◽  
Vol 73 (7) ◽  
pp. 945-956 ◽  
Author(s):  
Gerhard Skofitseh ◽  
Wolfgang Gubisch ◽  
Sunil J. Wimalawansa ◽  
David M. Jacobowitz

Using the indirect immunofluorescence method with a polyclonal antiserum raised in rabbits and directed against amylin (AMY), we have investigated the distribution of AMY-like immunoreactivity (-ir) throughout the central nervous system of the rat. The widespread distribution of AMY-ir was much more abundant than that previously reported for calcitonin gene related peptide (CGRP) immunoreactivity. In most brain areas there was no overlap between AMY- and CGRP-ir cell body groupings, with the exception of the motor nuclei of the hindbrain and spinal cord, which were found to contain large numbers of AMY- and CGRP-immunoreactive cell bodies. Areas with a moderate to dense appearance of AMY-ir were the rhinencephalon, the nucleus of the diagonal band, the magnocellular, dorso- and ventro-medial and mammillary nuclei of the hypothalamus, the habenula, the compact part of the substantia nigra, the ruber and pontine nuclei, and the inferior olive and the cerebellar nuclei. The widespread immunohistochemical distribution of AMY-ir in the rat brain is in partial agreement with the distribution of AMY-binding sites.Key words: calcitonin gene related peptide, amylin, central nervous system, immunohistochemistry, rat.


Cephalalgia ◽  
2018 ◽  
Vol 39 (3) ◽  
pp. 403-419 ◽  
Author(s):  
Erica R Hendrikse ◽  
Rebekah L Bower ◽  
Debbie L Hay ◽  
Christopher S Walker

Background Calcitonin gene-related peptide is an important target for migraine and other painful neurovascular conditions. Understanding the normal biological functions of calcitonin gene-related peptide is critical to understand the mechanisms of calcitonin gene-related peptide-blocking therapies as well as engineering improvements to these medications. Calcitonin gene-related peptide is closely related to other peptides in the calcitonin gene-related peptide family of peptides, including amylin. Relatedness in peptide sequence and in receptor biology makes it difficult to tease apart the contributions that each peptide and receptor makes to physiological processes and to disorders. Summary The focus of this review is the expression of calcitonin gene-related peptide, related peptides and their receptors in the central nervous system. Calcitonin gene-related peptide is expressed throughout the nervous system, whereas amylin and adrenomedullin have only limited expression at discrete sites in the brain. The components of two receptors that respond to calcitonin gene-related peptide, the calcitonin gene-related peptide receptor (calcitonin receptor-like receptor with receptor activity-modifying protein 1) and the AMY1 receptor (calcitonin receptor with receptor activity-modifying protein 1), are expressed throughout the nervous system. Understanding expression of the peptides and their receptors lays the foundation for more deeply understanding their physiology, pathophysiology and therapeutic use.


1987 ◽  
Vol 17 (6) ◽  
pp. 327-337 ◽  
Author(s):  
Yasuhiko Okimura ◽  
Kazuo Chihara ◽  
Hiromi Abe ◽  
Tetsuya Kita ◽  
Yoichi Kashio ◽  
...  

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