Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior |
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| Authors: | David-Marian Otte Maria Luisa Barcena de Arellano Andras Bilkei-Gorzo ?nder Albayram Sophie Imbeault Haang Jeung Judith Alferink Andreas Zimmer |
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| Institution: | 1. Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.; 2. Department of Psychiatry, University of Bonn, Bonn, Germany.; McLean Hospital/Harvard Medical School, United States of America, |
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| Abstract: | NMDA receptors are activated after binding of the agonist glutamate to the NR2 subunit along with a co-agonist, either L-glycine or D-serine, to the NR1 subunit. There is substantial evidence to suggest that D-serine is the most relevant co-agonist in forebrain regions and that alterations in D-serine levels contribute to psychiatric disorders. D-serine is produced through isomerization of L-serine by serine racemase (Srr), either in neurons or in astrocytes. It is released by astrocytes by an activity-dependent mechanism involving secretory vesicles. In the present study we generated transgenic mice (SrrTg) expressing serine racemase under a human GFAP promoter. These mice were biochemically and behaviorally analyzed using paradigms of anxiety, depression and cognition. Furthermore, we investigated the behavioral effects of long-term administration of D-serine added to the drinking water. Elevated brain D-serine levels in SrrTg mice resulted in specific behavioral phenotypes in the forced swim, novelty suppression of feeding and olfactory bulbectomy paradigms that are indicative of a reduced proneness towards depression-related behavior. Chronic dietary D-serine supplement mimics the depression-related behavioral phenotype observed in SrrTg mice. Our results suggest that D-serine supplementation may improve mood disorders. |
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