Blocking of striated muscle degeneration by serotonin in C. elegans.
Prevention of muscle fiber degeneration is a key issue in the treatment of muscular dystrophies such as Duchenne Muscular Dystrophy (DMD). It is widely postulated that existing pharmaceutical compounds might potentially be beneficial to DMD patients, but tools to identify them are lacking. Here, by using a Caenorhabditis elegans model of dystrophin-dependent muscular dystrophy, we show that the neurohormone serotonin and some of its agonists are potent suppressors of muscle degeneration. Inhibitors of serotonin reuptake transporters, which prolong the action of endogenous serotonin, have a similar effect. Moreover, reduction of serotonin levels leads to degeneration of non-dystrophic muscles. Our results demonstrate that serotonin is critical to C. elegans striated muscles. These findings reveal a new function of serotonin in striated muscles.
Carre-Pierrat
Maité
M
CGMC, CNRS-UMR 5534, Université Lyon 1, 43 bld du 11 Novembre, 69622 Villeurbanne Cedex, France.
Mariol
Marie-Christine
MC
Chambonnier
Lucie
L
Laugraud
Aurélie
A
Heskia
Fabienne
F
Giacomotto
Jean
J
Ségalat
Laurent
L
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism; D012701:Serotonin / Q000627:therapeutic use*; D018490:Serotonin Agents / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
D029742:Caenorhabditis elegans Proteins; D016189:Dystrophin; D012701:Serotonin; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493229:mod-5 protein, C elegans