Altered Trek-1 Function in Sortilin Deficient Mice Results in Decreased Depressive-Like Behavior

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 de...

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Bibliographic Details
Published in:Frontiers in pharmacology 2018-08, Vol.9, p.863-863
Main Authors: Moreno, Sébastien, Devader, Christelle M, Pietri, Mariel, Borsotto, Marc, Heurteaux, Catherine, Mazella, Jean
Format: Article
Language:English
Subjects:
behavior
depression
electrophysiology
Life Sciences
Neurobiology
Neurons and Cognition
Pharmacology
sortilin
TREK-1
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Summary: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 ( ). To characterize the consequences of sortilin deletion on TREK-1 activity, we combined behavioral, electrophysiological and biochemical approaches performed and . Analyses of mice revealed that they display: (1) a corticosterone-independent anxiety-like behavior, (2) a resistance to depression as demonstrated by several behavioral tests, and (3) an increased activity of dorsal raphe nucleus neurons. All these properties were associated with TREK-1 action deficiency consequently to a decrease of its cell surface expression and to the modification of its electrophysiological activity. An increase of BDNF expression through activation of the furin-dependent constitutive pathway as well as an increase of the activated BDNF receptor TrkB were in agreement with the decrease of depressive-like behavior of mice. Our results demonstrate that the TREK-1 expression and function are altered in the absence of sortilin confirming the importance of this channel in the regulation on the mood as a crucial target to treat depression.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2018.00863