Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
Psychiatric Neuromodulation Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
Sci Rep. 2021 Mar 1;11(1):4910. doi: 10.1038/s41598-021-83998-0.
Microglial cells are affected in Alzheimer's disease (AD) and interact with amyloid-beta (Aβ) plaques. Apart from memory loss, depression is common in patients with AD. Electroconvulsive therapy (ECT) is an anti-depressive treatment that may stimulate microglia, induce neuroinflammation and alter the levels of soluble Aβ, but the effects of ECT on microglia and Aβ aggregation in AD are not known. We investigated the short- and long-term effects of ECT on neuroinflammation and Aβ accumulation. 5xFAD mice received either electroconvulsive stimulation (ECS n = 26) or sham treatment (n = 25) for 3 weeks. Microglia and Aβ were analyzed in samples collected 24 h, 5 weeks, or 9 weeks after the last treatment. Aβ plaques and microglia were quantified using immunohistochemistry. The concentration of soluble Aβ and cytokines was quantified using ELISA and levels of Aβ aggregates were measured with Western Blot. Microglial phagocytosis of Aβ in the hippocampus was evaluated by flow cytometry in Methoxy-X04 injected mice 24 h following the last ECS treatment. Y-maze and Elevated plus maze were performed to study behavior after 5 weeks. We could not detect any significant short- or long-term effects of ECS on Aβ pathology or neuroinflammation, but ECS reduced abnormal behavior in the Elevated Plus maze.
小胶质细胞在阿尔茨海默病（AD）中受到影响，并与淀粉样蛋白-β（Aβ）斑块相互作用。除了记忆丧失外，抑郁症在 AD 患者中很常见。电惊厥疗法（ECT）是一种抗抑郁治疗方法，它可能会刺激小胶质细胞，引发神经炎症并改变可溶性 Aβ的水平，但 ECT 对 AD 中小胶质细胞和 Aβ聚集的影响尚不清楚。我们研究了 ECT 对神经炎症和 Aβ积累的短期和长期影响。5xFAD 小鼠接受电惊厥刺激（ECS，n=26）或假处理（n=25）3 周。在最后一次治疗后 24 小时、5 周或 9 周收集样本，分析小胶质细胞和 Aβ。使用免疫组织化学定量 Aβ斑块和小胶质细胞。使用 ELISA 定量可溶性 Aβ和细胞因子的浓度，并使用 Western Blot 测量 Aβ 聚集物的水平。在最后一次 ECS 治疗后 24 小时，用 Methoxy-X04 注射小鼠通过流式细胞术评估海马体中 Aβ的小胶质细胞吞噬作用。在 5 周后进行 Y 迷宫和高架十字迷宫实验以研究行为。我们未检测到 ECS 对 Aβ 病理学或神经炎症有任何明显的短期或长期影响，但 ECS 减少了高架十字迷宫中的异常行为。
