一項(xiàng)刊登在PNAS上的研究發(fā)現(xiàn),，不可預(yù)測(cè)的長期壓力可能減少一種基因的表達(dá),，這種基因幫助防止涉及情緒障礙的一種大腦細(xì)胞萎縮,。神經(jīng)可塑性是指大腦細(xì)胞對(duì)新的體驗(yàn)做出響應(yīng)而重新組織的能力,，許多研究已經(jīng)把大腦海馬區(qū)的可塑性減少與長期壓力聯(lián)系了起來,。
Ronald Duman及其同事研究了一種維持可塑性且被抗抑郁藥物上調(diào)的基因“neuritin”的表達(dá)水平的減少是否會(huì)導(dǎo)致抑郁癥狀,。這組作者使用一個(gè)大鼠模型發(fā)現(xiàn)了不可預(yù)測(cè)的長期壓力減少了neuritin在海馬區(qū)的表達(dá),，而抗抑郁藥物的治療逆轉(zhuǎn)了這種效應(yīng)。此外,，這組作者證明了增加neuritin的表達(dá)直接防止了情緒障礙以及抑郁和焦慮相關(guān)行為的典型的大腦細(xì)胞萎縮,。
這組作者報(bào)告說，相反,，在實(shí)驗(yàn)中降低了neuritin水平的大鼠表現(xiàn)出了類似于長期不可預(yù)測(cè)的壓力引發(fā)的抑郁樣行為,。把這些結(jié)合起來，這些發(fā)現(xiàn)提示隨著時(shí)間推移,，重復(fù)的壓力可能產(chǎn)生導(dǎo)致海馬區(qū)神經(jīng)元萎縮的neuritin缺乏,，因此也就增加了對(duì)焦慮和情緒障礙的易感性。（生物谷Bioon.com）
doi:10.1073/pnas.1201191109
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Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress
Hyeon Sona,b,1, Mounira Banasra, Miyeon Choib, Seung Yeon Chaeb, Pawel Licznerskia, Boyoung Leea, Bhavya Voletia, Nanxin Lia, Ashley Lepacka, Neil M. Fourniera, Ka Rim Leeb, In Young Leeb, Juhyun Kimc, Joung-Hun Kimc, Yong Ho Kimd, Sung Jun Junge, and Ronald S. Dumana,1
Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressant treatment reverses this effect. We also show that viral-mediated expression of neuritin in the hippocampus produces antidepressant actions and prevents the atrophy of dendrites and spines, as well as depressive and anxiety behaviors caused by CUS. Conversely, neuritin knockdown produces depressive-like behaviors, similar to CUS exposure. The ability of neuritin to increase neuroplasticity is confirmed in models of learning and memory. Our results reveal a unique action of neuritin in models of stress and depression, and demonstrate a role for neuroplasticity in antidepressant treatment response and related behaviors.
