Svenningsson Per, Chergui Karima, Rachleff Ilan, Flajolet Marc, Zhang Xiaoqun, El Yacoubi Malika, Vaugeois Jean-Marie, Nomikos George G, Greengard Paul
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021, USA.
Science. 2006 Jan 6;311(5757):77-80. doi: 10.1126/science.1117571.
The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients. Overexpression of p11 increases 5-HT1B receptor function in cells and recapitulates certain behaviors seen after antidepressant treatment in mice. p11 knockout mice exhibit a depression-like phenotype and have reduced responsiveness to 5-HT1B receptor agonists and reduced behavioral reactions to an antidepressant.
尽管血清素信号传导异常被认为与抑郁症有关，但其病理生理学仍然是个谜。我们发现血清素1B受体[5-羟色胺（5-HT1B）受体]与p11相互作用。p11增加了5-HT1B受体在细胞表面的定位。在啮齿动物大脑中，抗抑郁药或电休克疗法会使p11增加，但在抑郁症动物模型和抑郁症患者的脑组织中p11会减少。p11的过表达会增强细胞中5-HT1B受体的功能，并重现小鼠接受抗抑郁治疗后出现的某些行为。p11基因敲除小鼠表现出类似抑郁症的表型，对5-HT1B受体激动剂的反应性降低，对抗抑郁药的行为反应也减少。
