"Opposing effects of catecholaminergic and serotoninergic system C.elegans: Potential implications for human posttraumatic stress disorders"

BLANCO MG; VEUTHEY T; ANDERSEN N; RAYES D; DE ROSA MJ

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

Reunión Conjunta de Sociedades de Biociencias.

Post-traumatic stressdisorders (PTSDs) is a clinical condition characterized by recurrent disruptingmemories of a traumatic event, hyperarousal and anxiety. Despite it is knownthat PTSD patients exhibit high levels of catecholamines (CA), even in the absenceof stress, the neural mechanisms underlying this condition is not completelyunderstood. The only 2 drugs approved for PTSD treatment, are selectiveserotonin (5-HT) reuptake inhibitors (SSRIs). The role of 5-HT in PTSD and its relationship with CA is very difficult to studyin the complex human nervous system (NS). C.elegans is suited to provide fundamental insights into the crosstalkbetween 5-TH and CA as its NS is simple, has a defined neural wiring diagram andconserved neurotransmitter systems. Moreover, as in mammals, C. elegans coordinates stress responseby releasing tyramine (TA) and octopamine (OA), which are structural andfunctional counterparts of CA, the mammalian ?fight or flight? hormones.We here studied parametersthat, in C. elegans, depends on 5-HTsuch as egg laying, pharyngeal pumping and letargus. We exposed tdc-1 and tbh-1 null mutants (unable to synthetize TA and OA, respectively)to exogenous 5-HT. We found that these mutants are hypersensitive to 5-TH. Moreover,we observed a reduction in the pharyngeal pumping rate in tph-1 null mutants (unable to synthetize 5-HT), which is partiallyrescued in tph-1;tbh-1 doublemutants. These results strongly suggest that 5-HT acts antagonistically to CAin C. elegans. These opposite actionscould be conserved in mammals and explain the efficiency of SSRIs in PTSDtreatment. We are now digging into the molecular and cellular underpinning ofthese antagonistic effects by analyzing mutants in serotonin receptors (many ofthem homologous to human 5ht receptors). This study will widen the  understanding of the  mechanisms involved in neuronal regulation ofstress response and could also provide new insights for PTDS treatment.