Departments of Psychology and Neuroscience.
Biology.
Neuroreport. 2022 Aug 3;33(11):476-480. doi: 10.1097/WNR.0000000000001808. Epub 2022 Jun 29.
Seizures induce brain region-dependent enhancements in microglia/macrophage activation. Neuronal subset-specific phosphatase and tensin homolog (PTEN) knockout (KO) mice display hyperactive mammalian target of rapamycin (mTOR) signaling in the hippocampus, cerebellum, and cortex followed by seizures that increase in severity with age. To determine if KO mice also exhibit alterations in the spatiotemporal activation pattern of microglia, we used flow cytometry to compare the percentage of major histocompatibility complex-II activated microglia/macrophages between KO and wildtype (WT) mice at 5, 10, and 15 weeks of age. At 5 weeks, microglia/macrophage activation was greater in the cortex, P < 0.001, cerebellum, P < 0.001, and hippocampus, P < 0.001, of KO compared to WT mice. At 10 weeks, activation was greatest in the cortex of KO mice, P < 0.001, in the cerebellum of WT mice, P < 0.001, but similar in the hippocampus, P > 0.05. By 15 weeks, activation in the hippocampus was more than 25 times greater in KO mice compared to WT mice, P < 0.001. We show that hyperactive mTOR signaling is associated with an altered spatiotemporal pattern of microglia/macrophage activation in the brain and induces an enhanced neuroimmune response in the hippocampus.
癫痫诱导脑区依赖的小胶质细胞/巨噬细胞激活增强。神经元亚群特异性磷酸酶和张力蛋白同源物（PTEN）敲除（KO）小鼠在海马体、小脑和皮质中显示出过度活跃的哺乳动物雷帕霉素靶蛋白（mTOR）信号，随后癫痫发作的严重程度随年龄增加而增加。为了确定 KO 小鼠是否也表现出小胶质细胞时空激活模式的改变，我们使用流式细胞术比较了 5、10 和 15 周龄 KO 和野生型（WT）小鼠大脑中主要组织相容性复合体-II 激活的小胶质细胞/巨噬细胞的百分比。在 5 周时，KO 小鼠的皮质、小脑和海马体中的小胶质细胞/巨噬细胞激活程度明显更高，P < 0.001、P < 0.001 和 P < 0.001。在 10 周时，KO 小鼠的皮质激活程度最大，P < 0.001，WT 小鼠的小脑激活程度最大，P < 0.001，但海马体的激活程度相似，P > 0.05。到 15 周时，KO 小鼠的海马体激活程度比 WT 小鼠高 25 倍以上，P < 0.001。我们表明，过度活跃的 mTOR 信号与大脑中小胶质细胞/巨噬细胞激活的时空模式改变有关，并在海马体中诱导增强的神经免疫反应。
