| First Author | Otte DM | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 6 | Pages | e67131 |
| PubMed ID | 23805296 | Mgi Jnum | J:204204 |
| Mgi Id | MGI:5529841 | Doi | 10.1371/journal.pone.0067131 |
| Citation | Otte DM, et al. (2013) Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior. PLoS One 8(6):e67131 |
| abstractText | 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. |
