van Buel E M, Bosker F J, van Drunen J, Strijker J, Douwenga W, Klein H C, Eisel U L M
Department of Molecular Neurobiology, Groningen Institute of Evolutionary Life Sciences, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, Netherlands.
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
J Neuroinflammation. 2015 Dec 12;12:232. doi: 10.1186/s12974-015-0454-x.
Long-term neuroimmune activation is a common finding in major depressive disorder (MDD). Literature suggests a dual effect of electroconvulsive therapy (ECT), a highly effective treatment strategy for MDD, on neuroimmune parameters: while ECT acutely increases inflammatory parameters, such as serum levels of pro-inflammatory cytokines, there is evidence to suggest that repeated ECT sessions eventually result in downregulation of the inflammatory response. We hypothesized that this might be due to ECT-induced attenuation of microglial activity upon inflammatory stimuli in the brain.
Adult male C57Bl/6J mice received a series of ten electroconvulsive seizures (ECS) or sham shocks, followed by an intracerebroventricular (i.c.v.) lipopolysaccharide (LPS) or phosphate-buffered saline (PBS) injection. Brains were extracted and immunohistochemically stained for the microglial marker ionized calcium-binding adaptor molecule 1 (Iba1). In addition, a sucrose preference test and an open-field test were performed to quantify behavioral alterations.
LPS induced a short-term reduction in sucrose preference, which normalized within 3 days. In addition, LPS reduced the distance walked in the open field and induced alterations in grooming and rearing behavior. ECS did not affect any of these parameters. Phenotypical analysis of microglia demonstrated an LPS-induced increase in microglial activity ranging from 84 to 213 % in different hippocampal regions (CA3 213 %; CA1 84 %; dentate gyrus 131 %; and hilus 123 %). ECS-induced alterations in microglial activity were insignificant, ranging from -2.6 to 14.3 % in PBS-injected mice and from -20.2 to 6.6 % in LPS-injected mice.
We were unable to demonstrate an effect of ECS on LPS-induced microglial activity or behavioral alterations.
长期神经免疫激活是重度抑郁症（MDD）的常见表现。文献表明，电休克疗法（ECT）作为治疗MDD的一种高效策略，对神经免疫参数具有双重作用：虽然ECT会急性增加炎症参数，如促炎细胞因子的血清水平，但有证据表明，重复进行ECT最终会导致炎症反应下调。我们推测，这可能是由于ECT诱导大脑中炎症刺激下小胶质细胞活性减弱所致。
成年雄性C57Bl/6J小鼠接受一系列十次电惊厥发作（ECS）或假电击，随后进行脑室内（i.c.v.）注射脂多糖（LPS）或磷酸盐缓冲盐水（PBS）。提取大脑并对小胶质细胞标志物离子钙结合衔接分子1（Iba1）进行免疫组织化学染色。此外，进行蔗糖偏好试验和旷场试验以量化行为改变。
LPS导致蔗糖偏好短期降低，3天内恢复正常。此外，LPS减少了旷场中的行走距离，并诱导了梳理和站立行为的改变。ECS对这些参数均无影响。小胶质细胞的表型分析表明，LPS诱导不同海马区域（CA3为213%；CA1为84%；齿状回为131%；海马 hilus为123%）的小胶质细胞活性增加。ECS诱导的小胶质细胞活性改变不显著，在注射PBS的小鼠中为-2.6%至14.3%，在注射LPS的小鼠中为-20.2%至6.6%。
我们未能证明ECS对LPS诱导的小胶质细胞活性或行为改变有影响。
