生活中,，人們每天都要面對各種各樣的壓力，有的人神經(jīng)“大條”,，能坦然面對,；有的人則惶惶不安，進而患上抑郁癥,、焦慮癥等精神疾病,。這種差異背后的病理機制尚不清楚。而日前一國際研究小組發(fā)表在《自然》雜志上的報告稱,，是人大腦中的neuropsin蛋白活性決定了應激行為的模式,，該蛋白信號通路讓某些人在壓力面前更顯脆弱。
該研究小組由來自英國,、日本和波蘭的神經(jīng)系統(tǒng)科學家組成,。經(jīng)過四年研究，他們發(fā)現(xiàn)，人在感到壓力時,，大腦杏仁核會產(chǎn)生更多的neuropsin蛋白,，從而觸發(fā)一系列化學反應，進而激活與應激行為機制相關的基因,。通過實驗,，研究人員證明了neuropsin蛋白通路與應激行為模式的關系。
研究人員將小鼠放到一個迷宮式空間中來觀察其應激行為模式,。他們發(fā)現(xiàn),，在開放的、光照強烈的地方,，小鼠會感到壓力而惶恐不安,，并想辦法逃離；而當通過藥物或者基因手段抑制了小鼠大腦杏仁核生成neuropsin蛋白的功能后,，它們在同樣的區(qū)域就不會再有類似的應激行為模式出現(xiàn)。研究人員得出結(jié)論,，是neuropsin蛋白活性決定了小鼠的抗壓能力,，進而決定了它的應激行為模式。
研究人員認為,，人大腦中的neuropsin蛋白通路也起著相同的作用,，決定了人的應激行為模式。這一信號通路的發(fā)現(xiàn),，為預防和治療與壓力相關的精神疾病,，如抑郁癥、創(chuàng)傷后遺癥等,，提供了新的可能性,，而要開發(fā)出可實際應用的干預療法，控制應激行為,，還需要作進一步的研究,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
