The background potassium channel TREK-1 has been shown to be a potent target for depression treatment. Indeed, deletion of this channel in mice resulted in a depression resistant phenotype. The association of TREK-1 with the sorting protein sortilin prompted us to investigate the behavior of mice deleted from the gene encoding sortilin ().
View Article and Find Full Text PDFInhibition of the potassium channels TREK-1 by spadin (SPA) is currently thought to be a promising therapeutic target for the treatment of depression. Since these channels are expressed in pancreatic -cells, we investigated their role in the control of insulin secretion and glucose homeostasis. In this study, we confirmed the expression of TREK-1 channels in the insulin secreting MIN6-B1 -cell line and in mouse islets.
View Article and Find Full Text PDFThe neuropeptide neurotensin (NT) elicits numerous pharmacological effects through three different receptors (NTSR1, NTSR2, and NTSR3 also called sortilin). Pharmacological approaches and generation of NTSR1 and NTSR2-deficient mice allowed to determine the NT-induced antipsychotic like behavior, the inhibitory of weak fear memory and the nociceptive signaling in a rat formalin tonic pain model to NTSR1. Conversely, the effects of NT on thermal and tonic nociceptions were mediated by NTSR2.
View Article and Find Full Text PDFBackground: Despite intense research on mechanisms underlying the depressive pathophysiology, reliable biomarkers to assess antidepressant treatment response are still lacking. Since the sortilin-derived propeptide (PE) displays potent antidepressant activities and can be measured in the blood of rodents, we wondered whether in human its seric level can vary between patients affected by major depressive disorder (MDD) and healthy controls and after antidepressant treatment.
Methods: By using a specific dosing method, characterized by structure-recognition analysis with various synthesized PE analogues, we conducted a translational study to test whether blood levels of PE are under pathophysiological regulation and could serve as biomarkers of the depression state.
The aim of the present review is to unravel the mechanisms of action of the soluble form of the neurotensin (NT) receptor-3 (NTSR3), also called Sortilin, in numerous physiopathological processes including cancer development, cardiovascular diseases and depression. Sortilin/NTSR3 is a transmembrane protein thought to exert multiple functions both intracellularly and at the level of the plasma membrane. The Sortilin/NTSR3 extracellular domain is released by shedding from all the cells expressing the protein.
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