Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior.
Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior.
复制标题
慢性D链升高对抑郁症和焦虑相关行为动物模型的影响。
DOI：
10.1371/journal.pone.0067131
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zimmer A
中科院分区：
文献类型：
--
作者：
Otte DM;Barcena de Arellano ML;Bilkei-Gorzo A;Albayram O;Imbeault S;Jeung H;Alferink J;Zimmer A
NMDA受体在激动剂谷氨酸与NR 2亚基沿着与共激动剂（L-甘氨酸或D-丝氨酸）与NR 1亚基结合后被激活。有大量证据表明，D-丝氨酸是前脑区域中最相关的共激动剂，并且D-丝氨酸水平的改变有助于精神疾病。在神经元或星形胶质细胞中，D-丝氨酸通过丝氨酸消旋酶（Srr）异构化L-丝氨酸而产生。它由星形胶质细胞通过涉及分泌囊泡的活性依赖性机制释放。在本研究中，我们产生的转基因小鼠（SrrTg）表达丝氨酸消旋酶下的人GFAP启动子。使用焦虑、抑郁和认知的范例对这些小鼠进行生化和行为分析。此外，我们研究了长期服用添加到饮用水中的D-丝氨酸的行为影响。SrrTg小鼠脑D-丝氨酸水平升高导致强迫游泳中的特定行为表型，喂养和嗅球切除术范例的新奇性抑制，这表明抑郁相关行为的倾向性降低。慢性膳食D-丝氨酸补充剂模拟在SrrTg小鼠中观察到的抑郁症相关行为表型。我们的研究结果表明，D-丝氨酸补充剂可以改善情绪障碍。
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.
登录
查看更多内容
影响因子：
2.5
作者：
Baptista, V;Varanda, WA
通讯作者：
Varanda, WA
影响因子：
11
作者：
Basu, A. C.;Tsai, G. E.;Coyle, J. T.
通讯作者：
Coyle, J. T.
影响因子：
4.7
作者：
HALLERMAYER, K;HARMENING, C;HAMPRECHT, B
通讯作者：
HAMPRECHT, B
影响因子：
4
作者：
Benneyworth MA;Li Y;Basu AC;Bolshakov VY;Coyle JT
通讯作者：
Coyle JT
影响因子：
64.8
作者：
通讯作者：
--