生物谷：來自中科院上海生物化學與細胞生物學研究院，上海南方模式生物研究中心（Shanghai Nan Fang Model Organism Research Center）,，上海交通大學等處的研究人員發(fā)現了γ-氨基丁酸（γ-Aminobutyric acid,，GABA）轉運蛋白1（transporter subtype 1，GAT1）在調控神經狀態(tài)（mental status）方面的作用,，為研究GAT1在氨基丁酸系統(tǒng)（GABAergic systems）方面的功能提供了重要信息,，這一研究成果公布在Neuropsychopharmacology雜志上。
文章的通訊作者是來自中科院上海細胞生物學研究所的費儉博士,，其早年畢業(yè)于華東理工大學,，曾受邀赴香港中文大學、德國馬普生物物理研究所和悉尼大學進行合作研究,。
γ-氨基丁酸（γ-Aminobutyric acid,，GABA）轉運蛋白1（transporter subtype 1，GAT1）的作用主要是將細胞外的GABA轉運進突觸前神經細胞（presynaptic neurons）,，這在氨基丁酸系統(tǒng)（GABAergic systems）中起著重要的調控作用,。但是GAT1在調控神經狀態(tài)（mental status）方面的功能了解的并不全面。
在這篇文章中,，研究人員利用幾種depression-和 anxiety-小鼠模型觀察了GAT1敲除小鼠（GAT1 knockout,，GAT1-/-）的行為改變，比如強迫游泳試驗 (Forced Swimming Test, FST),，尾吊實驗（tail-suspension test）,，動物敞箱試驗(open-field test）等。結果他們發(fā)現GAT1-/-小鼠比較于野生型小鼠,，具有更低的depression-和anxiety-行為,，而且GAT1-/-小鼠對于篩選性抗抑郁劑，和抗焦慮藥,，比如fluoxetine, amitriptyline, buspirone, diazepam等呈現出可測量性的insensitivity,。這些研究數據都說明GAT1的缺失可以通過加強氨基丁酸系統(tǒng)來影響精神狀態(tài)，并且修改小鼠中serotonergic系統(tǒng),，和下丘腦-垂體-腎上腺(hypothalamic pituitary adrenal,，HPA)活性。
原始出處:
Neuropsychopharmacology (2007) 32, 1531–1539; doi:10.1038/sj.npp.1301281; published online 13 December 2006
Reduced Anxiety and Depression-Like Behaviors in Mice Lacking GABA Transporter Subtype 1
Guo-Xiang Liu1,2, Guo-Qiang Cai1, You-Qing Cai1,2,3, Zhe-Jin Sheng1, Jie Jiang1, Zhengtong Mei1, Zhu-Gang Wang3,4, Lihe Guo1 and Jian Fei1,3,4
1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Model Organism Research Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
2Graduate School of Chinese Academy of Sciences, Beijing, China
3Shanghai Nan Fang Model Organism Research Center, Pu Dong, Shanghai, China
4Model Organism Division, E-institutes of Shanghai Universities, Shanghai Jiao Tong University, Shanghai, China
Correspondence: Dr J Fei, Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Model Organism Research Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, No 7 Building, 319 Yue Yang Road, Shanghai 200031, China. Tel: +86 21 54920376; Fax: +86 21 58951005; E-mail: [email protected]
Received 30 March 2006; Revised 29 September 2006; Accepted 2 October 2006; Published online 13 December 2006.
-Aminobutyric acid (GABA) transporter subtype 1 (GAT1), which transports extracellular GABA into presynaptic neurons, plays an important regulatory role in the function of GABAergic systems. However, the contributions of the GAT1 in regulating mental status are not fully understood. In this paper, we observed the behavioral alterations of GAT1 knockout (GAT1-/-) mice using several depression- and anxiety-related models (eg, the forced-swimming test and the tail-suspension test for testing depression-related behaviors; the open-field test, the dark–light exploration test, the emergence test, and the elevated plus maze (EPM) test for anxiety-related behaviors). Here we found that GAT1-/- mice showed a lower level of depression- and anxiety-like behaviors in comparison to wild-type mice. Furthermore, GAT1-/- mice exhibited measurable insensitivity to selected antidepressants and anxiolytics such as fluoxetine, amitriptyline, buspirone, diazepam, and tiagabine in the tail-suspension test and/or the EPM test. Moreover, the basal level of corticosterone was found to be significantly lower in GAT1-/- mice. These results showed that the absence of GAT1 affects mental status through enhancing the GABAergic system, as well as modifying the serotonergic system and the hypothalamic-pituitary-adrenal (HPA) activity in mice.
Keywords:
GABA transporter 1, depression, anxiety, knockout mouse
