Riluzole promotes survival of rat motoneurons in vitro by stimulating trophic 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 cultures. Astrocyte monolayers prepared from new-born rats were exposed to vehicle or riluzole (1-10 microM) for 30-36 h, then washed and further incubated without riluzole for 24 h in L15 medium to obtain the astrocyte conditioned media (ACM). Motoneuron-enriched cultures were used to test the ability of the ACM to support motoneuron viability. Astrocyte monolayers exposed to 1 microM riluzole did not show changes in morphology or in DNA or protein synthesis. However, the conditioned medium obtained from astrocyte monolayers after this treatment increased motoneuron survival compared to that from vehicle-treated cultures. A similar effect was found when astrocytes were exposed to a higher riluzole concentration (10 microM) but with greater dilutions of the conditioned medium. This trophic activity was abolished by boiling or after treatment with trypsin. These findings strongly suggest the existence of a new trophic mechanism, through which riluzole may exert motoneuron protection.
Peluffo
H
H
Instituto Clemente Estable and Facultad de Ciencias, Montevideo, Uruguay.
Estevez
A
A
Barbeito
L
L
Stutzmann
J M
JM
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis; D007150:Immunohistochemistry; D007930:Leucine / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis; D019782:Riluzole; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D017475:Receptors, Nerve Growth Factor; D013844:Thiazoles; D019782:Riluzole; D004247:DNA; D007930:Leucine; D013936:Thymidine