کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2200925 1099986 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Levels of d-serine in the brain and peripheral organs of serine racemase (Srr) knock-out mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Levels of d-serine in the brain and peripheral organs of serine racemase (Srr) knock-out mice
چکیده انگلیسی

d-Serine, an endogenous co-agonist of the N-methyl-d-aspartate (NMDA) receptor, plays an important role in mammalian brain neurotransmission, via the NMDA receptor. d-Serine is synthesized from l-serine by the pyridoxal-5′ phosphate-dependent enzyme serine racemase (SRR), and d-serine is metabolized by d-amino acid oxidase (DAAO). In this study, we measured levels of the neurotransmission related amino acids, d-serine, l-serine, glycine, glutamine and glutamate in the frontal cortex, hippocampus, striatum and cerebellum as well as in peripheral tissues of blood, heart, pancreas, spleen, liver, kidney, testis, epididymis, heart, lung, muscle and eyeball, in wild-type (WT) and Srr-knockout (Srr-KO) mice. Levels of d-serine in the frontal cortex, hippocampus, and striatum of Srr-KO mice were significantly lower than in WT mice, while levels in the cerebellum stayed the same. In contrast, levels of l-serine, glycine, glutamine and glutamate remained the same in all tested brain regions. In vivo microdialysis using free-moving mice showed that extracellular levels of d-serine in the hippocampus of Srr-KO mice were significantly lower than in WT mice while the other amino acid levels remained the same between mice. In peripheral organs, levels of d-serine in the kidney, testis, and muscle of Srr-KO mice were significantly lower than in WT mice. Tissue levels of the other tested amino acids in peripheral organs were not altered. These results suggest that SRR is the major enzyme responsible for d-serine production in the mouse forebrain, and that other pathways of d-serine production may exist in the brain and peripheral organs.


► d-Serine is synthesized from l-serine by serine racemase (SRR).
► Levels of d-serine are decreased in the forebrain of Srr-KO mice.
► Approximately 10–20% of d-serine of wild type mice was detected in the forebrain of Srr-KO mice.
► SRR is the major enzyme responsible for d-serine production in the mouse forebrain.
► Other pathways of d-serine production may exist in the brain and peripheral organs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 59, Issue 6, November 2011, Pages 853–859
نویسندگان
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