Modulation of D-serine levels in brains of mice lacking PICK1
Modulation of D-serine levels in brains of mice lacking PICK1
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DOI：
10.1016/j.biopsych.2007.09.025
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发表时间：
2008-05-15
影响因子：
10.6
通讯作者：
Sawa, Akira
中科院分区：
文献类型：
--
作者：
Hikida, Takatoshi;Mustafa, Asif K.;Sawa, Akira
背景：D-丝氨酸是N-甲基-D-天冬氨酸亚型谷氨酸受体的内源性促凝剂。遗传关联的研究有牵连的基因编码的酶与D-丝氨酸代谢在精神分裂症和双相disorder.Methods：丝氨酸消旋酶（SR）和它的结合伙伴，蛋白质相互作用与C-激酶（PICK 1），蛋白质表达进行了检查，从野生型和PICK 1基因敲除小鼠的大脑。D-丝氨酸在野生型和PICK 1小鼠的水平也检查了由一个建立的高压液相色谱protocol.Results：SR和PICK 1蛋白的表达发育调节。虽然没有观察到SR蛋白水平的变化，D-丝氨酸的水平被选择性地降低，在新生的PICK 1基因敲除小鼠的前脑，与野生型mice.Conclusions：PICK 1可能参与脑D-丝氨酸水平和SR的调节在空间和时间上的特定方式。
Background: D-serine is an endogenous coagonist of the N-methyl-D-aspartate subtype glutamate receptor. Genetic association studies have implicated genes coding for enzymes associated with D-serine metabolism in schizophrenia and bipolar disorder.Methods: Protein expression of serine racemase (SR) and its binding partner, protein interacting with C-kinase (PICK1), were examined by Western blotting in brains from wildtype and PICK1 knockout mice. Levels of D-serine in wildtype and PICK1 mice were also examined by an established high-pressure liquid chromatography protocol.Results: Expression of SR and PICK1 proteins was developmentally regulated. Although no change was observed in the level of SR protein, levels of D-serine were selectively decreased in the forebrain of neonatal PICK1 knockout mice, compared with those in wildtype mice.Conclusions: PICK1 may be involved in the regulation of brain D-serine levels and SR in a spatially and temporally specific manner.