RILUZOLE PROMOTES SURVIVAL OF RAT MOTONEURONS IN-VITRO BY STIMULATINGTROPHIC ACTIVITY PRODUCED BY SPINAL ASTROCYTE MONOLAYERS

In the present study we have assessed whether riluzole stimulates the production of trophic activities for motoneurons by spinal astrocyte c ultures. Astrocyte monolayers prepared from new-born rats were exposed to vehicle or riluzole (1-10 mu M) for 30-36 h, then washed and furth er incubated without riluzole for 24 h in L15 medium to obtain the ast rocyte conditioned media (ACM). Motoneuron-enriched cultures were used to test the ability of the ACM to support motoneuron viability. Astro cyte monolayers exposed to 1 mu M riluzole did not show changes in mor phology or in DNA or protein synthesis. However, the conditioned mediu m obtained from astrocyte monolayers after this treatment increased mo toneuron survival compared to that from vehicle-treated cultures. A si milar effect was found when astrocytes were exposed to a higher riluzo le concentration (10 mu M) but with greater dilutions of the condition ed medium. This trophic activity was abolished by boiling or after tre atment with trypsin. These findings strongly suggest the existence of a new trophic mechanism, through which riluzole may exert motoneuron p rotection. (C) 1997 Elsevier Science Ireland Ltd.