Limoa Erlyn, Hashioka Sadayuki, Miyaoka Tsuyoshi, Tsuchie Keiko, Arauchi Ryosuke, Azis Ilhamuddin A, Wake Rei, Hayashida Maiko, Araki Tomoko, Furuya Motohide, Liaury Kristian, Tanra Andi J, Horiguchi Jun
Department of Psychiatry, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, 693-8501, Japan.
Department of Psychiatry, Hasanuddin University Faculty of Medicine, Jl. Perintis Kemerdekaan Km. 10, Makassar, 90245, South Sulawesi, Indonesia.
J Neuroinflammation. 2016 Sep 2;13(1):230. doi: 10.1186/s12974-016-0688-2.
Although electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats.
The rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively.
We found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats.
ECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.
尽管电休克治疗（ECT）被视为治疗难治性精神障碍的有效方法之一，但其治疗作用机制仍不清楚。最近，许多研究表明ECT会影响免疫相关细胞，如小胶质细胞、星形胶质细胞和淋巴细胞。此外，小胶质细胞激活和星形胶质细胞激活与精神分裂症患者的死后大脑有关。我们之前证明，Gunn大鼠表现出类似精神分裂症的行为且大脑中有小胶质细胞激活。本研究检测了电休克（ECS，ECT的动物对应模型）对Gunn大鼠大脑中类似精神分裂症行为、小胶质细胞增生和星形胶质细胞增生的影响。
将大鼠分为四组，即Wistar假手术组、Wistar ECS组、Gunn假手术组和Gunn ECS组。ECS组连续六天每天接受一次ECS。随后，进行前脉冲抑制（PPI）测试，并分别使用抗CD11b和抗胶质纤维酸性蛋白（GFAP）抗体进行免疫组织化学分析，以确定海马体中小胶质细胞和星形胶质细胞的激活程度。
我们发现与Wistar大鼠相比，Gunn大鼠存在PPI缺陷，而ECS可使其显著改善。免疫组织化学分析显示，与Wistar大鼠相比，Gunn大鼠中CD11b和GFAP的免疫反应性显著增加。ECS显著减弱了Gunn大鼠中CD11b和GFAP的免疫反应性。
ECS改善了Gunn大鼠的类似精神分裂症行为，并减轻了Gunn大鼠海马体中的小胶质细胞增生和星形胶质细胞增生。因此，ECT的治疗效果可能至少部分是通过抑制胶质细胞激活来实现的。这些结果可能为阐明激活的胶质细胞在精神分裂症发病机制中的作用以及确定未来的治疗干预措施是否应尝试上调或下调胶质细胞功能提供关键信息。
