Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?
Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?
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DOI：
10.1016/j.nbd.2010.08.005
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发表时间：
2010-12
影响因子：
6.1
通讯作者：
Holmes, Andrew
中科院分区：
文献类型：
--
作者：
Fitzgerald, Paul J.;Barkus, Chris;Feyder, Michael;Wiedholz, Lisa M.;Chen, Yi-Chyan;Karlsson, Rose-Marie;Machado-Vieira, Rodrigo;Graybeal, Carolyn;Sharp, Trevor;Zarate, Carlos;Harvey-White, Judith;Du, Jing;Sprengel, Rolf;Gass, Peter;Bannerman, David;Holmes, Andrew
谷氨酸能功能障碍与精神分裂症和情绪障碍密切相关。GluA1基因敲除（KO）小鼠表现出精神分裂症和抑郁症相关的异常。在这里，我们询问GluA1 KO是否表现出躁狂相关的异常。测试了KO在接近/避免冲突测试中的行为，对反复强迫游泳暴露的反应，以及应激和精神兴奋剂治疗后的运动反应。观察快速多巴胺耗竭、锂或GSK-3β抑制剂治疗对KO运动亢进的影响。结果显示，KO表现出新颖性和压力诱导的运动过度活跃，强迫游泳不动减少，接近/避免冲突测试改变。精神兴奋剂治疗和多巴胺消耗加重了KO运动过度活跃。锂治疗，而不是GSK-3β抑制剂，使KO焦虑相关行为正常化，部分逆转了过度运动行为，也逆转了前额叶皮层磷酸化- marcks和磷酸化-神经调节素水平升高。总的来说，这些发现证明了GluA1 KO与躁狂症相关的异常，并结合先前的发现，表明该突变可能提供了一种新的分裂情感性障碍特征模型。
Glutamatergic dysfunction is strongly implicated in schizophrenia and mood disorders. GluA1 knockout (KO) mice display schizophrenia- and depression-related abnormalities. Here, we asked whether GluA1 KO show mania-related abnormalities. KO were tested for behavior in approach/avoid conflict tests, responses to repeated forced swim exposure, and locomotor responses under stress and after psychostimulant treatment. The effects of rapid dopamine depletion and treatment with lithium or GSK-3β inhibitor on KO locomotor hyperactivity were tested. Results showed that KO exhibited novelty- and stress-induced locomotor hyperactivity, reduced forced swim immobility and alterations in approach/avoid conflict tests. Psychostimulant treatment and dopamine depletion exacerbated KO locomotor hyperactivity. Lithium, but not GSK-3β inhibitor, treatment normalized KO anxiety-related behavior and partially reversed hyperlocomotor behavior, and also reversed elevated prefrontal cortex levels of phospho-MARCKS and phospho-neuromodulin. Collectively, these findings demonstrate mania-related abnormalities in GluA1 KO and, combined with previous findings, suggest this mutant may provide a novel model of features of schizoaffective disorder.
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影响因子：
1.6
作者：
Brigman, Jonathan L.;Mathur, Poonam;Holmes, Andrew
通讯作者：
Holmes, Andrew
影响因子：
2.9
作者：
Boyce-Rustay, Janel M.;Cameron, Heather A.;Holmes, Andrew
通讯作者：
Holmes, Andrew
影响因子：
7.6
作者：
Gould, Todd D.;O'Donnell, Kelley C.;Manji, Husseini K.
通讯作者：
Manji, Husseini K.
影响因子：
4.8
作者：
Chourbaji, S.;Vogt, M. A.;Gass, P.
通讯作者：
Gass, P.
影响因子：
2.9
作者：
GROENINK, L;VANDERGUGTEN, J;OLIVIER, B
通讯作者：
OLIVIER, B