Peluffo H, Estevez A, Barbeito L, Stutzmann J M
Instituto Clemente Estable and Facultad de Ciencias, Montevideo, Uruguay.
Neurosci Lett. 1997 Jun 13;228(3):207-11. doi: 10.1016/s0304-3940(97)00384-4.
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.
在本研究中，我们评估了利鲁唑是否能刺激脊髓星形胶质细胞培养物产生对运动神经元的营养活性。从新生大鼠制备的星形胶质细胞单层分别用溶剂或利鲁唑（1 - 10微摩尔）处理30 - 36小时，然后洗涤，并在不含利鲁唑的L15培养基中进一步孵育24小时，以获得星形胶质细胞条件培养基（ACM）。使用富含运动神经元的培养物来测试ACM支持运动神经元存活的能力。暴露于1微摩尔利鲁唑的星形胶质细胞单层在形态、DNA或蛋白质合成方面未显示出变化。然而，与溶剂处理的培养物相比，此处理后从星形胶质细胞单层获得的条件培养基提高了运动神经元的存活率。当星形胶质细胞暴露于更高浓度的利鲁唑（10微摩尔）但条件培养基稀释度更高时，也发现了类似的效果。这种营养活性通过煮沸或用胰蛋白酶处理后被消除。这些发现强烈表明存在一种新的营养机制，利鲁唑可能通过该机制发挥对运动神经元的保护作用。
