Chronic inhibitory effect of riluzole on trophic factor production.

Chronic inhibitory effect of riluzole on trophic factor production. Exp Neurol. 2015 Jun 10; Authors: Dennys CN, Armstrong J, Levy M, Byun YJ, Ramdial KR, Bott M, Rossi FH, Fernández-Valle C, Franco MC, Estevez AG Abstract Riluzole is the only FDA approved drug for the treatment of amyotrophic lateral sclerosis (ALS). However, the drug affords moderate protection to ALS patients, extending life for a few months by a mechanism that remains controversial. In the presence of riluzole, astrocytes increase the production of factors protective to motor neurons. The stimulation of trophic factor production by motor neuron associated cells may contribute to riluzole's protective effect in ALS. Here, we investigated the effects of media conditioned by astrocytes and Schwann cells acutely or chronically incubated with riluzole on trophic factor-deprived motor neuron survival. While acute riluzole incubation induced CT-1 secretion by astrocytes and Schwann cells, chronic treatment stimulated a significant decrease in trophic factor production compared to untreated cultures. Accordingly, conditioned media from astrocytes and Schwann cells acutely treated with riluzole protected motor neurons from trophic factor deprivation-induced cell death. Motor neuron protection was prevented by incubation with CT-1 neutralizing antibodies. In contrast, conditioned media from astrocytes and Schwann cells chronically treated with riluzole was not protective....
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research