耶魯大學(xué)醫(yī)學(xué)院的研究人員的一項(xiàng)新研究顯示,，他們使大腦中的一種運(yùn)動(dòng)相關(guān)基因充當(dāng)了強(qiáng)大的抗抑郁劑。這一發(fā)現(xiàn)可能提供了一種新的抗抑郁藥物靶標(biāo),。這些結(jié)果是通過對(duì)小鼠進(jìn)行研究獲得的,，相關(guān)文章發(fā)表在新一期的《自然—醫(yī)學(xué)》（Nature Medicine）上。
負(fù)責(zé)這項(xiàng)研究的Ronald Duman教授表示,，VGF訓(xùn)練相關(guān)基因和藥物研發(fā)靶標(biāo)將比化學(xué)抗抑郁劑更好,，因?yàn)樗呀?jīng)存在于大腦中了,。
據(jù)調(diào)查，在美國有16%的人口受到抑郁癥的影響,，并且每年與此相關(guān)的花費(fèi)高達(dá)830億美元?，F(xiàn)有的抗抑郁癥藥物能夠幫助其中65%的患者，并且需要用藥數(shù)周至數(shù)月的時(shí)間,。
Duman指出,，已經(jīng)知道運(yùn)動(dòng)能夠改善大腦功能和心理健康，并且在發(fā)生大腦損傷或腦病時(shí)能夠?qū)Υ竽X起到保護(hù)作用,，但是對(duì)大腦中的這種作用是如何發(fā)生的卻知之甚少,。他表示，由于現(xiàn)有藥物需要服用的時(shí)間太長,，因此研究一些神經(jīng)元的適應(yīng)性或可塑性是必要的,。
他和他的研究組設(shè)計(jì)出了一種特制的芯片來分析基因表達(dá)中的細(xì)小變化，尤其是大腦的海馬體區(qū)域中的變化,。而海馬體則對(duì)壓力激素,、抑郁和抗抑郁劑高度敏感。
接著,，他們比較了久坐（極少運(yùn)動(dòng)）小鼠的大腦活動(dòng)和運(yùn)動(dòng)多的小鼠進(jìn)行比較,。研究人員觀察到，踩輪子的小鼠每晚相當(dāng)于走六英里的距離,。四個(gè)獨(dú)立的芯片分析實(shí)驗(yàn)確定出33個(gè)海馬體運(yùn)動(dòng)調(diào)節(jié)基因,，其中27個(gè)基因是新鑒定出的基因。
其中,，VGF基因通過運(yùn)動(dòng)提升得最為明顯,。而且，VGF的功能就好比一種強(qiáng)大的抗抑郁劑,，而抑制VGF就會(huì)抵銷運(yùn)動(dòng)的效果,，并且誘導(dǎo)出小鼠的類抑郁癥行為。
原始出處:
Nature Medicine
Published online: 2 December 2007 | doi:10.1038/nm1669
Antidepressant actions of the exercise-regulated gene VGF
Joshua G Hunsberger1, Samuel S Newton1, Alicia H Bennett1, Catharine H Duman1, David S Russell1, Stephen R Salton2 & Ronald S Duman1
Abstract
Exercise has many health benefits, including antidepressant actions in depressed human subjects, but the mechanisms underlying these effects have not been elucidated. We used a custom microarray to identify a previously undescribed profile of exercise-regulated genes in the mouse hippocampus, a brain region implicated in mood and antidepressant response. Pathway analysis of the regulated genes shows that exercise upregulates a neurotrophic factor signaling cascade that has been implicated in the actions of antidepressants. One of the most highly regulated target genes of exercise and of the growth factor pathway is the gene encoding the VGF nerve growth factor, a peptide precursor previously shown to influence synaptic plasticity and metabolism. We show that administration of a synthetic VGF-derived peptide produces a robust antidepressant response in mice and, conversely, that mutation of VGF in mice produces the opposite effects. The results suggest a new role for VGF and identify VGF signaling as a potential therapeutic target for antidepressant drug development.
Department of Psychiatry, Yale University, 34 Park Street, New Haven, Connecticut 06508 USA.
Fishberg Department of Neuroscience, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029, USA.
Correspondence to: Ronald S Duman1 e-mail: [email protected]
