Molecular biological study on the pathophysiology of bipolar disorders

我们检测了双相情感障碍和重度抑郁障碍患者和正常对照组的thapsigargin(微粒体钙-三磷酸腺苷酶抑制剂)诱导的一过性血小板内钙升高(TCI)和碳酸钙内流(CCE)。三组间thapsigargin诱导的TCI或CCE差异无统计学意义。而在双相障碍中，蛋白激酶C(PKC)激动剂对CCE的抑制作用增强，而PKC抑制剂对CCE的刺激作用减弱。钙调蛋白抑制剂的作用在三组间无显著差异。这些结果表明，双相情感障碍患者的PKC功能得到了代偿性增强，以维持细胞内钙浓度的动态平衡。作为双相情感障碍的少数生物标志物之一，增强了外周血细胞中各种激动剂的钙动员作用。最近，内质网应激反应中的关键基因XBP1的多态性被证明与双相情感障碍的遗传危险因素有关。因此，在本研究中，我们研究了健康受试者血小板中XBP1基因多态性与钙信号转导的关系。本研究结果表明，在-116C/C、C/G、G/G三种基因型的正常人中，基础钙水平或5-羟色胺诱导的钙动员无显著差异。

We examined thapsigargin (microsomal Ca-ATPase inhibitor)-induced transient intraplatelet calcium increase (TCI) and capcitative calcium entry (CCE) in the patients with bipolar disorder and major depressive disorder, and normal controls. There was no significant difference in thapsigargin-induced TCI or CCE among the three groups. However, in bipolar disorders, the inhibitory effect of proteinkinase C (PKC) stimulator on CCE was increased, and the stimulatory effect of PKC inhibitor on CCE was decreased. No significant differences in the effect of calmodulin inhibitor were observed among the three groups. These results suggest that the PKC function in bipolar disorders is compensatively enhanced to maintain the homeostasis of intracellular calcium (Ca) concentrations.Enhanced Ca mobilization to various agonists in peripheral blood cells in one of a few confirmed biological markers for bipolar disorders. Recently, a polymorphism of XBP1, a pivotal gene in the endoplasmic reticulum stress response, was shown to contribute to the genetic risk factor for bipolar disorder. Thus, in this study, we examined the relationship between the XBP1 gene polymorphism and the Ca signaling in the platelets of healthy subjects. The present results suggest no significant difference in the basal Ca level or serotonin-induced Ca mobilization among normal subjects with -116C/C, C/G, G/G genotypes.