Influence of glial-derived matrix molecules, especially chondroitin sulfates, on neurite growth and survival of cultured mouse embryonic motoneurons.

摘要

Mechanisms controlling neuronal survival and regeneration play an important role during development, after birth, and under lesion conditions. Isolated embryonic mouse motoneurons have been a useful tool for studying such basic mechanisms. These cultured motoneurons depend on extracellular matrix (ECM) molecules, which are potent mediators of survival and axonal growth and guidance in the CNS and in vitro, exhibiting either attractive or repellent guidance cues. Additionally, ECM proteoglycans and glycoproteins are components of the glial scar acting as a growth barrier for regenerating axons. Compared with CNS axon outgrowth, less is known about the cues that guide motoneurons toward their peripheral targets. Because we are interested in the effects of glial-derived chondroitin sulfate proteoglycans (CSPGs), we have worked out a model system for investigating the influences of glial-derived matrix molecules on motoneuron outgrowth and survival. We used cultured embryonic mouse motoneurons to investigate axon growth effects of matrix molecules produced by the glial-derived cell lines A7, Neu7, and Oli-neu primary astrocytes as well as the immortalized Schwann cell line IMS32. The results indicate that molecules of the ECM, especially chondroitin sulfates, play an important role as axon growth-promoting cues. We could demonstrate a modifying effect of the matrix components on motoneuron survival and caspase3-induced apoptosis.