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Le récepteur 3 de la neurotensine/Sortiline dans la régulation de l’état dépressif

Abstract : Major depressive disorder is a condition that affects 20% of the population and is the leading cause of morbidity and disability worldwide. Recently, the TREK-1 potassium channel has been shown to be a potential target in the treatment of depression. The deletion of this channel or its blocking by a derived peptide resulting from the maturation of Sortilin, propeptide (PE), or its synthetic analogue Spadin, results in a phenotype of resistance to depression in mice. Sortilin is a protein able to bind with TREK-1 but also with the neurotrophic factor BDNF, an important factor for neuronal viability and depressive state regulation. Sortilin is therefore involved in regulating the intracellular addressing of TREK-1 and BDNF. Initially, my work focused on the consequences of the deletion of the Sortilin gene (sort1-/-) on the TREK-1 and BDNF addressing, and the neurotensinergic system. The results showed a decrease in TREK-1 membrane expression at the cerebral level and an increase in BDNF. All of these changes lead the Sort1-/- mice to develop a phenotype of resistance to depression. In addition, these mice show an increase in brain neurotensin concentration and its receptor 2, leading to increased resistance to pain perception. In a second phase, I was interested in whether PE, a potential antidepressant, showed serum variations in depressed patients and could be an indicator of depressive syndrome. We showed that the serum PE level is significantly reduced in depressed people, a level restored after treatment with antidepressants. In conclusion, Sortilin plays a major key in the regulation of depressive disorder and also in nociception.
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Submitted on : Wednesday, March 21, 2018 - 4:12:36 PM
Last modification on : Wednesday, October 14, 2020 - 4:22:18 AM
Long-term archiving on: : Thursday, September 13, 2018 - 10:43:51 AM


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  • HAL Id : tel-01740184, version 1



Sébastien Moreno. Le récepteur 3 de la neurotensine/Sortiline dans la régulation de l’état dépressif. Biologie cellulaire. Université Côte d'Azur, 2017. Français. ⟨NNT : 2017AZUR4136⟩. ⟨tel-01740184⟩



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