Retroinverso analogs of spadin display increased antidepressant effects
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- 作者：Julie Veyssiere (1) (2)
Hamid Moha ou Maati (1) (2) (3)
Jean Mazella (1) (2)
Georges Gaudriault (4)
S茅bastien Moreno (1) (2)
Catherine Heurteaux (1) (2)
Marc Borsotto (1) (2)
1. Universit茅 de Nice Sophia Antipolis ; IPMC ; 06560 ; Sophia Antipolis ; France
2. CNRS ; IPMC ; 06560 ; Sophia Antipolis ; France
3. Institut de G茅nomique Fonctionnelle ; 141 rue de la Cardonille ; 34095 ; Montpellier Cedex 5 ; France
4. Medincell SA ; 1 rue Charles Cros ; 34830 ; Jacou ; France - 关键词：Retro ; inverso ; Spadin ; TREK ; 1 ; Depression ; Electrophysiology
- 刊名：Psychopharmacology
- 出版年：2015
- 出版时间：February 2015
- 年：2015
- 卷：232
- 期：3
- 页码：561-574
- 全文大小：2,663 KB
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- 刊物主题：Biomedicine
Pharmacology and Toxicology
Psychiatry - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-2072
文摘
Rationale Although depression is the most common mood disorder, only one third of patients are treated with success. Finding new targets, new drugs, and also new drug intake way are the main challenges in the depression field. Several years ago, we identified a new target with the TWIK-related potassium channel-1 (TREK-1) potassium channel, and more recently, we have discovered a peptide of 17 amino acids with antidepressant properties. This peptide, that we called spadin, can be considered as a new concept in antidepressant drug design. Spadin derives from a larger peptide resulting to a posttranslational maturation of sortilin; consequently, spadin can be considered as a natural molecule. Moreover, spadin acts more rapidly than classical antidepressants and does not induce side effects. Objectives In this work, we sought analogs of spadin displaying a better affinity on TREK-1 channels and an increased action duration. Methods Analogs were characterized by electrophysiology measurements, by behavioral tests, and by their ability to induce neurogenesis. Results We identified two retro-inverso peptides that have kept the antidepressant properties of spadin; particularly, they increased the hippocampal neurogenesis after a 4-day treatment. As spadin, these analogs did not induce side effects on either pain, epilepsy processes, or at the cardiac level. Conclusions Together, our results indicated that spadin retro-inverso peptides could represent new potent antidepressant drugs. As exemplified by spadin in the field of depression, retro-inverso strategies could represent a useful technique for developing new classes of drugs in a number of pathologies.