The cystine/glutamate antiporter as a potential novel target to modulate the stress response?

Thomas Demuyser, Eduard Mihai Bentea, Lauren Deneyer, Giulia Albertini, Joeri Van Liefferinge, Ellen Merckx, Ann Massie, Ilse Julia Smolders

Research output: Chapter in Book/Report/Conference proceedingMeeting abstract (Book)


Introduction: In modern society, stress is a major causative factor for a variety of psychiatric disorders. Depression, one of the main causes of disability worldwide, is a multimodal disease with chronic stress considered as a ‘trigger’ for depressive episodes. Depression and comorbid anxiety are usually related to a malfunctioning monoaminergic system, nowadays however compelling evidence points at an important role of glutamate in the etiology of the ‘depressed/anxious brain’. Being the major excitatory neurotransmitter in the central nervous system, glutamate can potentially have important excitotoxic effects. System xc- is the cystine/glutamate antiporter and the major source of extrasynaptic glutamate in some important depression-related brain areas, where it can be an interesting new target for improved psychopharmacological treatment.

Methods: In this study we investigated the effect of loss of functional system xc- (e.g. deletion of the specific light chain subunit xCT; xCT-/-), on chronic stress induced depression and anxiety in a validated animal model. Therefore we subjected xCT-/- and xCT+/+ mice, treated with chronic corticosterone injections (excessive chronic stress), to a battery of acute stress-based tests for depressive- and anxiety- like behavior and compared their behavior to vehicle treated and naïve animals.

Results and discussion: Interestingly we found decreased depressive- and anxiety- like behavior in the naïve xCT-/- mice in all of the tests conducted. Unexpectedly however the decrease in depressive- and anxiety- like behavior faded and disappeared after vehicle and corticosterone treatment. These findings support further research for the role of system xc- in the stress response, since the involvement of the antiporter in regulating the response to acute versus chronic stress seems to differ.

Research support: This research was supported by the Fund for Scientific Research Flanders (FWO, grant G.038412N), the Queen Elisabeth Medical Foundation (G.S.K.E.), and the Vrije Universiteit Brussel (Strategic Research Program, grant SRP40).
Original languageEnglish
Title of host publicationStress and Behavior, 5th International Neuroscience and Biological Psychiatry Conference, June 22-24, 2015, Miami, USA
Publication statusPublished - 2015
Event5th International Regional Neuroscience and Biopsychiatry Conference - Stress and Behavior - Courtyard Miami Downtown, Miami, United States
Duration: 22 Jun 201524 Jun 2015


Conference5th International Regional Neuroscience and Biopsychiatry Conference - Stress and Behavior
Country/TerritoryUnited States


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