期刊
NEUROCHEMISTRY INTERNATIONAL
卷 75, 期 -, 页码 76-78出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2014.05.015
关键词
Serine racemase; Activity-regulated cytoskeleton-associated protein; Dendritic spines; Dentate gyrus; Schizophrenia
资金
- Phyllis 81 Jerome Lyle Rappaport Mental Health Research Scholars Award
- [1K99MH099252-01A1]
- [R01MH05190]
- [P50MH0G0450]
Activity-regulated cytoskeleton-associated protein (Arc) is an immediate early gene that is expressed almost exclusively in glutamatergic neurons. Arc protein is enriched in the postsynaptic density (PSD) and colocalizes with the N-methyl-D-aspartate receptor (NMDAR) complex. Arc transcription is positively modulated by NMDAR activity and is important for dendritic spine plasticity. Genetic ablation of serine racemase (SR-/-), the enzyme that converts L-serine to D-serine, a coagonist at the NMDAR, reduces dendritic spine density in the hippocampus. Here we demonstrate that SR deficient (SR-/-) mice also have reduced Arc protein expression in the hippocampus that can be reversed with chronic D-serine administration in adulthood. Furthermore, D-serine treatment partially rescues the hippocampal spine deficit in SR-/- mice. These results demonstrate the importance of D-serine in regulating the hippocampal expression of Arc in vivo. In addition, our findings underscore the potential utility of using the glycine modulatory site agonist D-serine to treat disorders that exhibit Arc and dendritic spine dysregulation as a consequence of NMDAR hypofunction, such as schizophrenia. (C) 2014 Elsevier Ltd. All rights reserved.
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