华人学者：发现“绝望”基因

　　

生物通报道，马尔兰大学药理学院的科学家jiapei Wang近期在BMC Neuroscience上发表PKCI/HINT1基因敲除的研究成果文章，Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level。

 

文章通讯作者是华人学者jiapei Wang教授，第一作者是她的博士后Elizabeth Barbier。

 

据文章介绍，一种组氨酸三聚体核苷结合蛋白Ⅰ（PKCI/HINT1）基因与抑郁和焦虑情绪有关。这是一个先前从未发现与情感障碍有关的基因。

 

对其进行功能研究发现，敲除KCI/HINT1基因的小鼠在行为上表现得更为积极、乐观。而表达该基因的小鼠的行为模式显得焦虑和抑郁，把小鼠放在强光照射或是水中时，小鼠表现出厌世的情绪，不主动争取脱离这种不良环境。而敲除了该基因的小鼠表现得更为积极主动，它会不停回避这类环境。

 

研究人员尚不清楚为何删除该基因会改变小鼠的情感状态，该基因编码的蛋白质可能作为抑郁症，双向情感障碍和分裂症的防治靶点。另外，该基因敲除小鼠可以作为研究躁狂症的模型。现在还没有可用于躁狂症的动物模型。

 

同样值得注意的是其他的研究发现双向障碍和分裂症患者尸体大脑中该基因编码的蛋白含量下降。

 

这可能是一个与精神分裂症，双向障碍和抑郁症有关的重要基因。 目前科学家还不清楚它是如何发挥作用的，这些机制的研究将成为科学家下一步的研究计划。

 

这是第一篇揭示KCI/HINT1基因在双向障碍和分裂症中重要性的文章。

（生物通 小茜）

Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level

Background

Protein kinase C interacting protein (PKCI/HINT1) is a small protein belonging to the histidine triad (HIT) family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO) mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models.  Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder.   We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT) littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA) axis function, we assessed the HPA activity through measurement of plasma corticosterone levels.

 

Results

Compared to the WT controls, KO mice exhibited less immobility in the forced swim (FST) and the tail suspension (TST) tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT. 

 

Conclusion

PKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma.  These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS.