Proteomics of serotonergic autoregulation

Serotonin regulates its own production, degradation and release in the Raphe nuclei of the brain mainly by modifying the level and activity of autoreceptors on serotonin-producing neurons, such as 5-HT1A and 5-HT1B. This autoregulation is probably the reason for the delayed response of patients with depression to the most common antidepressive drugs inhibiting the serotonin transporter (SERT), a molecule responsible for the reuptake of serotonin and therefore for its quick removal from the synaptic cleft. However, the signaling pathways involved in autoregulation and the molecular alterations induced by serotonin on its autoreceptors are yet unclear. We aim at analysing changes in levels of proteins induced by longterm changes of serotonin levels in Raphe nuclei of mice with low and elevated serotonin release in the brain to reveal the signaling pathways involved in the autoregulation of serotonergic neurons.