生物谷：来自中科院上海生物化学与细胞生物学研究院，上海南方模式生物研究中心（Shanghai Nan Fang Model Organism Research Center），上海交通大学等处的研究人员发现了γ-氨基丁酸（γ-Aminobutyric acid，GABA）转运蛋白1（transporter subtype 1，GAT1）在调控神经状态（mental status）方面的作用，为研究GAT1在氨基丁酸系统（GABAergic systems）方面的功能提供了重要信息，这一研究成果公布在Neuropsychopharmacology杂志上。
文章的通讯作者是来自中科院上海细胞生物学研究所的费俭博士，其早年毕业于华东理工大学，曾受邀赴香港中文大学、德国马普生物物理研究所和悉尼大学进行合作研究。
γ-氨基丁酸（γ-Aminobutyric acid，GABA）转运蛋白1（transporter subtype 1，GAT1）的作用主要是将细胞外的GABA转运进突触前神经细胞（presynaptic neurons），这在氨基丁酸系统（GABAergic systems）中起着重要的调控作用。但是GAT1在调控神经状态（mental status）方面的功能了解的并不全面。
在这篇文章中，研究人员利用几种depression-和 anxiety-小鼠模型观察了GAT1敲除小鼠（GAT1 knockout，GAT1-/-）的行为改变，比如强迫游泳试验 (Forced Swimming Test, FST)，尾吊实验（tail-suspension test），动物敞箱试验(open-field test）等。结果他们发现GAT1-/-小鼠比较于野生型小鼠，具有更低的depression-和anxiety-行为，而且GAT1-/-小鼠对于筛选性抗抑郁剂，和抗焦虑药，比如fluoxetine, amitriptyline, buspirone, diazepam等呈现出可测量性的insensitivity。这些研究数据都说明GAT1的缺失可以通过加强氨基丁酸系统来影响精神状态，并且修改小鼠中serotonergic系统，和下丘脑-垂体-肾上腺(hypothalamic pituitary adrenal，HPA)活性。
原始出处:
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: jfei@sibs.ac.cn
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
