生活中，人们每天都要面对各种各样的压力，有的人神经“大条”，能坦然面对；有的人则惶惶不安，进而患上抑郁症、焦虑症等精神疾病。这种差异背后的病理机制尚不清楚。而日前一国际研究小组发表在《自然》杂志上的报告称，是人大脑中的neuropsin蛋白活性决定了应激行为的模式，该蛋白信号通路让某些人在压力面前更显脆弱。

该研究小组由来自英国、日本和波兰的神经系统科学家组成。经过四年研究，他们发现，人在感到压力时，大脑杏仁核会产生更多的neuropsin蛋白，从而触发一系列化学反应，进而激活与应激行为机制相关的基因。通过实验，研究人员证明了neuropsin蛋白通路与应激行为模式的关系。

研究人员将小鼠放到一个迷宫式空间中来观察其应激行为模式。他们发现，在开放的、光照强烈的地方，小鼠会感到压力而惶恐不安，并想办法逃离；而当通过药物或者基因手段抑制了小鼠大脑杏仁核生成neuropsin蛋白的功能后，它们在同样的区域就不会再有类似的应激行为模式出现。研究人员得出结论，是neuropsin蛋白活性决定了小鼠的抗压能力，进而决定了它的应激行为模式。

研究人员认为，人大脑中的neuropsin蛋白通路也起着相同的作用，决定了人的应激行为模式。这一信号通路的发现，为预防和治疗与压力相关的精神疾病，如抑郁症、创伤后遗症等，提供了新的可能性，而要开发出可实际应用的干预疗法，控制应激行为，还需要作进一步的研究。

原文出处：

Nature  doi:10.1038/nature09938

Neuropsin cleaves EphB2 in the amygdala to control anxiety

Benjamin K. Attwood,1 Julie-Myrtille Bourgognon,1 Satyam Patel,1 Mariusz Mucha,1 Emanuele Schiavon,1 Anna E. Skrzypiec,1 Kenneth W. Young,2 Sadao Shiosaka,3 Michal Korostynski,4 Marcin Piechota,4 Ryszard Przewlocki4 & Robert Pawlak1

A minority of individuals experiencing traumatic events develop anxiety disorders. The reason for the lack of correspondence between the prevalence of exposure to psychological trauma and the development of anxiety is unknown. Extracellular proteolysis contributes to fear-associated responses by facilitating neuronal plasticity at the neuron–matrix interface1, 2, 3, 4. Here we show in mice that the serine protease neuropsin is critical for stress-related plasticity in the amygdala by regulating the dynamics of the EphB2–NMDA-receptor interaction, the expression of Fkbp5 and anxiety-like behaviour. Stress results in neuropsin-dependent cleavage of EphB2 in the amygdala causing dissociation of EphB2 from the NR1 subunit of the NMDA receptor and promoting membrane turnover of EphB2 receptors. Dynamic EphB2–NR1 interaction enhances NMDA receptor current, induces Fkbp5 gene expression and enhances behavioural signatures of anxiety. On stress, neuropsin-deficient mice do not show EphB2 cleavage and its dissociation from NR1 resulting in a static EphB2–NR1 interaction, attenuated induction of the Fkbp5 gene and low anxiety. The behavioural response to stress can be restored by intra-amygdala injection of neuropsin into neuropsin-deficient mice and disrupted by the injection of either anti-EphB2 antibodies or silencing the Fkbp5 gene in the amygdala of wild-type mice. Our findings establish a novel neuronal pathway linking stress-induced proteolysis of EphB2 in the amygdala to anxiety.