Sarrouilhe D, Dejean C
Laboratoire de physiologie humaine, faculté de médecine et pharmacie, université de Poitiers, 6, rue de la Milétrie, bâtiment D1, TSA 51115, 86073 Poitiers cedex 9, France.
Service de pharmacie, pavillon Janet, centre hospitalier Henri-Laborit, 370, avenue Jacques-Cœur, 86021 Poitiers cedex, France.
Rev Neurol (Paris). 2015 Nov;171(11):762-7. doi: 10.1016/j.neurol.2015.07.002. Epub 2015 Aug 28.
Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder.
重度抑郁症是一种多因素的慢性致残性情绪疾病，终生患病率高，且与过高的死亡率相关，尤其是心血管疾病导致的死亡以及自杀死亡。用三环类抗抑郁药和单胺氧化酶抑制剂治疗这种疾病的耐受性较差，而那些选择性靶向5-羟色胺和去甲肾上腺素再摄取的药物对所有患者都无效，这表明需要寻找新的治疗靶点。对重度抑郁症患者大脑的尸检研究表明，前额叶皮质和蓝斑中形成缝隙连接的膜蛋白连接蛋白30和连接蛋白43的表达降低。使用慢性不可预测应激（一种抑郁症啮齿动物模型）表明，星形胶质细胞缝隙连接功能障碍促成了重度抑郁症的病理生理学。用氟西汀长期治疗大鼠以及用阿米替林长期处理大鼠培养的皮质星形胶质细胞支持了这样的假说，即脑星形胶质细胞之间缝隙连接细胞间通讯的上调可能是抗抑郁药治疗作用的一种新机制。总之，星形胶质细胞缝隙连接正成为治疗重度抑郁症患者的一个新的潜在治疗靶点。
