J Neuro：日研究者发现两种蛋白质结合程度可诊断抑郁症

近日，日本一项新研究发现，分析血液中两种蛋白质的结合程度，就可以诊断是否患上抑郁症。这一发现有望促进开发出用于诊断抑郁症的试剂等，改善抑郁症诊断缺少客观指标，只能采用问诊的局面。
 
神经突触之间的神经传导物质血清素不足被认为是抑郁症的一个原因。此前研究发现，血清素被过多清除与一种载体蛋白质不分解有关，而这种载体蛋白质必须与一种泛素蛋白质结合才能分解。
 
名城大学研究人员在美国新一期《神经科学期刊》The Journal of Neuroscience上报告说，他们在研究中注意到，在血液中的淋巴细胞和血小板内，能够检测出血清素的载体蛋白质。研究人员分别从健康人、轻度抑郁症患者、重度抑郁症患者各6人体内采集了血样，对分离出的淋巴细胞进行分析研究。结果发现，轻度抑郁症患者这两种蛋白质的结合度与健康人相比要低约20%，而重度抑郁症患者则低约40%。
 
利用这种分析淋巴细胞的方法，得出结果需要两三天时间。为更快得出结果，研究人员目前正在研究对血清素载体蛋白质含量更高的血小板进行检测和分析的方法。研究人员表示今后准备与制药公司合作，开发出相关试剂。

doi:10.1523/​JNEUROSCI.6458-11.2012
PMC:
PMID:

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.