Ricerc@Sapienza

Depression is complex illness characterized by disruptions in the functioning of physiological, neuroendocrine and behavioural processes. Of these, sleep disturbance and circadian rhythm abnormalities constitute the most prevalent signs of depression. Prokineticin 2 (PROK2) is a new chemokine that binding to Prokineticin receptor 1 (PKR1) and 2 (PKR2), exerts numerous biological effects involved in pain, inflammatory processes, neurogenesis, behavior and circadian rhythms. Circadian rhythms are prominent in a variety of behavioral and physiological processes, including sleep/wake cycles, and disrupted circadian rhythms are strictly associated with major depression. PROK2/PKRs are highly expressed in the suprachiasmatic nucleus (SCN), the master pacemaker that drives circadian rhythms in mammals, and PKRs are expressed in all of the primary SCN target areas, most of which are involved in depression. Studies indicate that PROK2 signaling plays a critical role in the stress-related traits in mice and establish a possible molecular link between circadian rhythms and depression illness. Indeed, in wild type mice, central infusion of PROK2 let to increased anxiety and depression-like behaviors; in contrast, mice deficient in PROK2 or in PKR1 gene (preliminary data from our lab) display reduced anxiety and depression-like behaviors. In the present project we want to investigate the involvement of the prokineticin system in two animal models of depression. Considering that our research group have at its disposal an antagonist of the PKRs (PC1) we want to evaluate if blocking the PROK system, somehow targeting or affecting the circadian systems, could represent a new pharmacological strategy for the treatment of depression disorders. Another aspect that we want to investigate is to evaluate if targeting the PROK system, could lead to a more rapid onset of antidepressant effect that, still now, represents a very important limit of the available pharmacological treatments.