21 - Neuropeptide Synthesis in Astrocytes: Possible Trophic Roles

Abstract

Astrocyte expression of neuropeptide genes is not only gene-and brain region-specific but occurs early in CNS development. Both somatostatin (SS) and met-enkephalin (ME) peak in astrocytes derived from embryonic day 20 animals and decrease to adult levels by 8 days postnatally. SS mRNA in cerebellar astrocytes also decreases, paralleling what is seen in vivo, whereas proenkephalin mRNA increases 3-fold, in comparison with a 10-fold increase in vivo. In order to test the hypothesis that the astrocyte-derived ME may be acting as a trophic factor, newborn rat pups were treated with the opiate antagonist naltrexone for 7–14 days. Nerve growth factor decreased developmentally in cerebellar and striatal astrocytes prepared from control animals: the decrease was partially prevented in astrocytes prepared from naltrexone-treated animals. Opiate receptors could not be detected on the astrocytes, suggesting an indirect effect of the endogenous opioid peptides. Cerebellar granule cells prepared from naltrexone-treated animals were more differentiated, with an increased content of neurofilament and glutaminase mRNAs. Exposure of cerebellar granule cells to 100 nM SS had the same differentiating effect. These results suggest that the astrocyte-derived peptides may function as CNS modelling agents (SS stimulatory and enkephalins inhibitory) by affecting neurite extension and neuronal phenotype early in CNS development, in part through effects on neurotrophic factor synthesis.