Mathews R, Li P P, Young L T, Kish S J, Warsh J J
Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Biol Psychiatry. 1997 Mar 15;41(6):649-56. doi: 10.1016/S0006-3223(96)00113-8.
As disturbances in guanine nucleotide binding (G) protein-coupled phosphoinositide second messenger systems have been implicated in bipolar disorder, we examined whether the abundance of G alpha q/11 and phospholipase C (PLC)-beta 1 two key transducing proteins in this signaling pathway, are altered in this disorder. Compared with the controls, immunoreactive levels of G alpha q/11 were significantly elevated by 62% (p = .047) in occipital cortex of bipolar subjects. A similar increase (52%) in the PLC-beta 1 immunolabeling was also found in the occipital cortex of the bipolar subjects, but only reached marginal statistical significance (p = .07). In contrast, frontal and temporal cortex G alpha q/11 or PLC-beta 1 immunolabeling did not differ between bipolar and control subjects. Cerebral cortical immunoreactive levels of G beta 1 or G beta 2, included as a negative control, were not different between comparison groups. These findings support and extend earlier observations suggesting that disturbances in G protein-coupled second messenger signaling pathways may play an important role in the pathophysiology of bipolar affective disorder.
由于鸟嘌呤核苷酸结合（G）蛋白偶联磷酸肌醇第二信使系统紊乱与双相情感障碍有关，我们研究了该信号通路中两个关键转导蛋白Gαq/11和磷脂酶C（PLC）-β1的丰度在该疾病中是否发生改变。与对照组相比，双相情感障碍患者枕叶皮质中Gαq/11的免疫反应水平显著升高62%（p = 0.047）。在双相情感障碍患者的枕叶皮质中也发现PLC-β1免疫标记有类似的增加（52%），但仅达到边缘统计学意义（p = 0.07）。相比之下，双相情感障碍患者和对照组在额叶和颞叶皮质的Gαq/11或PLC-β1免疫标记没有差异。作为阴性对照的Gβ1或Gβ2的大脑皮质免疫反应水平在比较组之间没有差异。这些发现支持并扩展了早期的观察结果，表明G蛋白偶联第二信使信号通路紊乱可能在双相情感障碍的病理生理学中起重要作用。
