Effects of glycosaminoglycans and proteinase inhibitors on astroglia-induced detachment of cultured rat cerebellar neurons

Abstract

Neurons in mixed primary embryonic CNS cultures degenerate secondary to their detachment from the substratum. The present study demonstrates that in primary cultures of postnatal cerebellum, detachment of neurons can be prevented by antiproliferative drugs which inhibit the growth of astroglia. Several types of proteinase inhibitors did not affect the process of detachment. However, among several types of glycosaminoglycans, heparan sulfate and to a lesser degree heparin, could reversibly inhibit neuron detachment without causing morphological changes of astroglia. The enzymes heparitinase and heparinase caused neuron detachment but only within the first 24–48 hr after plating and not in older cultures. We conclude:(1) cerebellar interneurons in culture are not dependent on astroglia for their survival(2) astroglia are most probably responsible for neuron detachment via a membrane associated activity and(3) heparan sulfate-like glycosaminoglycans are important in neuronsubstratum attachment.