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E Housden

Publications and source records attributed to E Housden.

3 recordsLinked to original sources

The effects of protease inhibitors on axon growth through astrocytes.

We have shown in a previous paper (Devl Biol. 135, 449, 1989) that axons regenerating from postnatal neurons are unable to penetrate three-dimensional cultures of mature astrocytes, while axons from embryonic dorsal root ganglia (DRGs) and retina will grow through such cultures for considerable distances. We have now investigated the role of proteases in the penetration of three-dimensional astrocyte cultures by axons from embryonic DRGs. Embryonic DRGs were grown in association with three-dimensional astrocyte cultures, with astrocyte monolayers, and with-air dried collagen. The effects of inhibitors of the three families of proteases that have been shown to be involved in tumour cell invasion were investigated. The serine protease inhibitors EACA and Trasylol both reduced growth in three-dimensional astrocyte cultures to around 50% of control, but had little effect on growth on astrocyte monolayers or on collagen. TIMP, which inhibits collagenases, had no effect on growth on two- or three-dimensional cultures. Cbz-gly-phen-amide, an inhibitor of enteroproteases, reduced growth in all three types of culture.

Animals

The growth of axons in three-dimensional astrocyte cultures.

The environment of the adult central nervous system (CNS) does not support axon regeneration. We have been unable to replicate this behaviour using monolayer cultures of glia, so we have developed a technique for three dimensional culture of glial cells. We have examined the growth of axons from embryonic and postnatal retina and dorsal root ganglia (DRG's) through purified three-dimensional astrocyte cultures. Neither postnatal DRG's nor adult retina were able to grow axons through astrocytes from cultures 3 weeks or more old, although some DRG axons grew in astrocyte cultures which were 10 days or less old. However axons from embryonic DRG's and retina grew axons profusely into even elderly astrocyte cultures. All the tissues grew axons into three-dimensional Schwann cell cultures. The behaviour of axons in three-dimensional glial cultures therefore reproduces the behaviour of axons in vivo.

Age Factors