2012年8月14日 訊 /生物谷BIOON/ --嚴(yán)重抑郁癥或慢性壓力能夠?qū)е履X容量減少,，從而導(dǎo)致情感障礙和認(rèn)知障礙。如今，耶魯大學(xué)科學(xué)家們領(lǐng)導(dǎo)的一個(gè)研究小組發(fā)現(xiàn)這為何會發(fā)生的一個(gè)原因：單個(gè)基因開關(guān)觸發(fā)人大腦連接減少和模式動物產(chǎn)生抑郁。2012年8月12日，相關(guān)研究結(jié)果發(fā)表在Nature Medicine期刊上,。
這些發(fā)現(xiàn)表明這種被稱作轉(zhuǎn)錄因子的基因開關(guān)抑制幾個(gè)在腦細(xì)胞之間突觸連接的形成中發(fā)揮至關(guān)重要作用的基因的表達(dá)，從而能夠?qū)е虑邦~皮質(zhì)中腦容量減少,。
論文通信作者Ronald Duman教授說,，“我們想驗(yàn)證這種觀點(diǎn)：壓力導(dǎo)致人大腦突觸減少。我們證實(shí)當(dāng)這單個(gè)轉(zhuǎn)錄因子保被激活時(shí),，正常條件下參與情感和認(rèn)知的神經(jīng)環(huán)路受到破壞,。”
研究人員分析了抑郁癥病人和非抑郁癥病人的大腦組織樣品,，研究了不同的基因激活模式。抑郁癥病人的大腦表現(xiàn)出較低水平的基因表達(dá),，其中這些基因是大腦突觸功能和結(jié)構(gòu)所必需的,。論文第一作者Hyo Jung Kang發(fā)現(xiàn)至少5個(gè)這樣的基因能夠受到被稱作GATA1的單個(gè)轉(zhuǎn)錄因子的調(diào)控。當(dāng)這個(gè)轉(zhuǎn)錄因子被激活時(shí),，嚙齒動物表現(xiàn)出類似抑郁的癥狀,，這就提示著GATA1在神經(jīng)元之間連接的減少中發(fā)揮著作用，而且也在抑郁癥狀中發(fā)揮著作用,。
Duman推測到,，GATA1上的基因變異可能有朝一日有助于鑒定出哪些人有高風(fēng)險(xiǎn)患上嚴(yán)重抑郁癥或?qū)毫^為敏感。(生物谷Bioon.com)
本文編譯自Study finds how stress, depression can shrink the brain
doi: 10.1038/nm.2886
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Decreased expression of synapse-related genes and loss of synapses in major depressive disorder
Hyo Jung Kang, Bhavya Voleti, Tibor Hajszan, Grazyna Rajkowska, Craig A Stockmeier, Pawel Licznerski, Ashley Lepack, Mahesh S Majik, Lak Shin Jeong, Mounira Banasr, Hyeon Son & Ronald S Duman
revious imaging and postmortem studies have reported a lower brain volume and a smaller size and density of neurons in the dorsolateral prefrontal cortex (dlPFC) of subjects with major depressive disorder (MDD)1, 2. These findings suggest that synapse number and function are decreased in the dlPFC of patients with MDD. However, there has been no direct evidence reported for synapse loss in MDD, and the gene expression alterations underlying these effects have not been identified. Here we use microarray gene profiling and electron microscopic stereology to reveal lower expression of synaptic-function–related genes (CALM2, SYN1, RAB3A, RAB4B and TUBB4) in the dlPFC of subjects with MDD and a corresponding lower number of synapses. We also identify a transcriptional repressor, GATA1, expression of which is higher in MDD and that, when expressed in PFC neurons, is sufficient to decrease the expression of synapse-related genes, cause loss of dendritic spines and dendrites, and produce depressive behavior in rat models of depression.
