近日，日本一項(xiàng)新研究發(fā)現(xiàn)，分析血液中兩種蛋白質(zhì)的結(jié)合程度,，就可以診斷是否患上抑郁癥,。這一發(fā)現(xiàn)有望促進(jìn)開(kāi)發(fā)出用于診斷抑郁癥的試劑等，改善抑郁癥診斷缺少客觀指標(biāo),，只能采用問(wèn)診的局面。
神經(jīng)突觸之間的神經(jīng)傳導(dǎo)物質(zhì)血清素不足被認(rèn)為是抑郁癥的一個(gè)原因,。此前研究發(fā)現(xiàn),，血清素被過(guò)多清除與一種載體蛋白質(zhì)不分解有關(guān)，而這種載體蛋白質(zhì)必須與一種泛素蛋白質(zhì)結(jié)合才能分解,。
名城大學(xué)研究人員在美國(guó)新一期《神經(jīng)科學(xué)期刊》The Journal of Neuroscience上報(bào)告說(shuō),，他們?cè)谘芯恐凶⒁獾剑谘褐械牧馨图?xì)胞和血小板內(nèi),，能夠檢測(cè)出血清素的載體蛋白質(zhì),。研究人員分別從健康人、輕度抑郁癥患者,、重度抑郁癥患者各6人體內(nèi)采集了血樣,，對(duì)分離出的淋巴細(xì)胞進(jìn)行分析研究。結(jié)果發(fā)現(xiàn),，輕度抑郁癥患者這兩種蛋白質(zhì)的結(jié)合度與健康人相比要低約20%,，而重度抑郁癥患者則低約40%,。
利用這種分析淋巴細(xì)胞的方法,，得出結(jié)果需要兩三天時(shí)間。為更快得出結(jié)果,，研究人員目前正在研究對(duì)血清素載體蛋白質(zhì)含量更高的血小板進(jìn)行檢測(cè)和分析的方法。研究人員表示今后準(zhǔn)備與制藥公司合作,，開(kāi)發(fā)出相關(guān)試劑,。（生物谷Bioon.com）
doi:10.1523/JNEUROSCI.6458-11.2012
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MAGE-D1 Regulates Expression of Depression-Like Behavior through Serotonin Transporter Ubiquitylation
Akihiro Mouri1,6,*, Aya Sasaki2,3,*, Ken Watanabe2, Chiharu Sogawa4, Shigeo Kitayama4, Takayoshi Mamiya1, Yoshiaki Miyamoto5, Kiyofumi Yamada6, Yukihiro Noda7,8,9, and Toshitaka Nabeshima1,8,9
The ubiquitin–proteasome system (UPS) controls the stability of most cellular proteins. The polymorphism of UPS-related genes is associated with major depression disorder, but less is known about the molecule that plays a role in depression by modulating the UPS. Melanoma antigen gene-D1 (MAGE-D1) interacts with RING E3 ubiquitin ligase and is implicated in protein degradation. MAGE-D1 may thus play an important role in the CNS via ubiquitylation. Here, we clarified a novel role of MAGE-D1 in emotional functions, namely its modulation of ubiquitylation to the serotonin transporter (SERT). The MAGE-D1 knock-out and knockdown by small interfering RNA (siRNA) in the prefrontal cortex showed depression-like behavior, such as a decrease in exploratory behavior in both the home cage and novel apparatus, a decrease in social interaction, increased immobility time during forced swimming and tail suspension, and a decrease in sucrose preference without any anxiety, or cognitive or motor dysfunction. Acute and chronic (28 d) administration of sertraline (10 mg/kg) and imipramine (20 mg/kg) reversed all or part of depression-like behavior in knock-out mice. In these mice, the serotonergic function in the prefrontal cortex and hippocampus was hypoactive, accompanied by hyperexpression of SERT attributable to a decrease in ubiquitylation. Furthermore, MAGE-D1 binds to SERT via the necdin homology domain. MAGE-D1 overexpression in cells resulted in a decrease in serotonin uptake activity and the protein level of SERT but an increase in ubiquitylated SERT. Together, the present findings suggest a novel role for MAGE-D1 in depressive behaviors: modulating SERT ubiquitylation.
