Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 59, Issue -, Pages 49-58Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2015.01.010
Keywords
Anxiety; Depression; Sensorimotor; System xc; Vision; xCT
Funding
- Fund for Scientific Research Flanders (FWO) [G.038412N]
- Queen Elisabeth Medical Foundation (G.S.K.E.)
- Vrije Universiteit Brussel (Strategic Research Program) [SRP40]
- FWO
- agency for Innovation by Science and Technology (IWT)
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There is considerable preclinical and clinical evidence indicating that abnormal changes in glutamalergic signaling underlie the development of mood disorders. Astrocytic glutamate dysfunction, in particular, has been recently linked with the pathogenesis and treatment of mood disorders, including anxiety and depression. System xc- is a glial cystine/glutamate antiporter that is responsible for nonvesicular glutamate release in various regions of the brain. Although system xc- is involved in glutamate signal transduction, its possible role in mediating anxiety or depressive-like behaviors is currently unknown. In the present study, we phenotyped adult and aged system xc- deficient mice in a battery of tests for anxiety and depressive-like behavior (open field, light/dal-lc test, elevated plus maze, novelty suppressed feeding, forced swim test, tail suspension test). Concomitantly, we evaluated the sensoriniotor function of system xc- deficient mice, using motor and sensorimotor based tests (rotarod, adhesive removal test, nest building test). Finally, due to the presence and potential functional relevance of system xc- in the eye, we investigated the visual acuity of system xc- deficient mice (optomotor test). Our results indicate that loss of system xc- does not affect motor or sensorimotor function, in either adult or aged mice, in any of the paradigms investigated. Similarly, loss of system xc- does not affect basic visual acuity, in either adult or aged mice. On the other hand, in the open field and light /dark tests, and forced swim and tail suspension tests respectively, we could observe significant anxiolytic and anticlepressive-like effects in system xc- deficient mice that in certain cases (light/dark, forced swim) were age-dependent. These findings indicate that, under physiological conditions, nonvesicular glutamate release via system xc- mediates aspects of higher brain function related to anxiety and depression, but does not influence sensorimotor function or spatial vision. As such, modulation of system xc- might constitute the basis of innovative interventions in mood disorders. (C) 2015 Elsevier Inc. All rights reserved.
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