ASTROCYTES AND MICROGLIA AS POTENTIAL TARGETS FOR CALCITONIN-GENE-RELATED PEPTIDE IN THE CENTRAL-NERVOUS-SYSTEM

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.