Loss of system xc- induces antidepressant- and anxiolytic-like effects in mice

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)


Today, stress is a major causative factor for a variety of psychiatric disorders. Depression 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, 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 important depression-related brain areas.

In this study we investigated the effect of loss of system xc- (e.g. deletion of the specific light chain subunit xCT; xCT-/-), on chronic stress induced depression and anxiety. 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.
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 system xc- in the stress response, since the involvement of the antiporter in regulating the response to acute versus chronic stress seems to differ.
Original languageEnglish
Title of host publicationVUB PhD Day
Publication statusPublished - 2015
EventVUB DS-LSM PhD day Research Unlimited - Brussel, Belgium
Duration: 31 Mar 201531 Mar 2015


ConferenceVUB DS-LSM PhD day Research Unlimited


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