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KCC2 Manipulation Alters Features of Migrating Interneurons in Ferret Neocortex.
Cerebral Cortex ( IF 2.9 ) Pub Date : 2019-12-17 , DOI: 10.1093/cercor/bhz048
F T Djankpa 1, 2 , F Lischka 3 , M Chatterjee 3 , S L Juliano 1, 4
Affiliation  

KCC2 is a brain specific chloride-potassium cotransporter affecting neuronal development including migration and cellular maturation. It modulates chloride homeostasis influencing the switch of GABA from depolarizing to hyperpolarizing, which contributes to the cues that influence the termination of neuronal migration. The expression of KCC2 during migration of interneurons, therefore, correlates with the ability of these cells to respond to GABA as a stop signal. Manipulation of KCC2 in development can affect various aspects of migrating neurons, including the speed. We describe the effect of KCC2 downregulation and inhibition on features of migrating interneurons of normal ferret kits and those treated with methylazoxymethanol acetate, which increases KCC2. Treatment of organotypic cultures with Bisphenol A, an environmental toxin that alters gene expression, also downregulates KCC2 protein. In organotypic slices treated with the KCC2 antagonist VU0240551, chloride imaging shows inhibition of KCC2 via blockade of chloride flux. Time-lapse video imaging of organotypic cultures treated with either drug, shows a significant increase in the average speed, step size, and number of turns made by migrating neurons leaving the ganglionic eminence. Our findings demonstrate the harmful effect of environmental toxins on brain development and potential consequences in the pathogenesis of neurodevelopmental disorders.

中文翻译:


KCC2 操纵改变雪貂新皮质中迁移中间神经元的特征。



KCC2 是一种大脑特异性氯钾协同转运蛋白,影响神经元发育,包括迁移和细胞成熟。它调节氯稳态,影响 GABA 从去极化到超极化的转变,这有助于提供影响神经元迁移终止的线索。因此,中间神经元迁移过程中 KCC2 的表达与这些细胞响应 GABA 作为停止信号的能力相关。在发育过程中操纵 KCC2 可以影响神经元迁移的各个方面,包括速度。我们描述了 KCC2 下调和抑制对正常雪貂试剂盒和用甲基偶氮甲醇乙酸酯处理(可增加 KCC2)的雪貂试剂盒迁移中间神经元特征的影响。用双酚 A(一种改变基因表达的环境毒素)处理器官型培养物也会下调 KCC2 蛋白。在用 KCC2 拮抗剂 VU0240551 处理的器官切片中,氯离子成像显示通过阻断氯离子通量来抑制 KCC2。用这两种药物处理的器官型培养物的延时视频成像显示,离开神经节隆起的迁移神经元的平均速度、步长和圈数显着增加。我们的研究结果证明了环境毒素对大脑发育的有害影响以及神经发育障碍发病机制的潜在后果。
更新日期:2019-12-19
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