MEK/ERK Signaling Regulates Reconstitution of the Dopaminergic Nerve Circuit in the Planarian Dugesia japonica
MEK/ERK Signaling Regulates Reconstitution of the Dopaminergic Nerve Circuit in the Planarian Dugesia japonica
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DOI：
10.1007/s11064-020-03226-5
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发表时间：
2021-01-19
影响因子：
4.4
通讯作者：
Kitamura, Yoshihisa
中科院分区：
文献类型：
--
作者：
Hijioka, Masanori;Ikemoto, Yusuke;Kitamura, Yoshihisa
涡虫 Dugesia japonica 是一种扁虫，在人工截肢后可以自主再生自己的身体。最近的一份报告显示了丝裂原激活蛋白激酶/细胞外信号调节激酶（MEK/ERK）通路在真涡虫截肢后再生过程中头部形态发生中的作用；然而，神经元特异性再生机制尚未见报道。在此，研究了 MEK/ERK 通路是否参与涡虫的多巴胺能神经元再生。涡虫在截肢后14天内再生了身体；然而，头部区域的形态发生被MEK抑制剂U0126（3或10μM）抑制。此外，U0126 也减少了再生头部区域涡虫酪氨酸羟化酶 (DjTH) 阳性多巴胺能神经元的数量。 6-羟基多巴胺（6-OHDA）是一种多巴胺能神经毒素，可以减少多巴胺能神经元的数量；然而，涡虫在将 6-OHDA 注射到肠道后可以再生多巴胺能神经元。 MEK抑制剂PD98059（30μM）或U0126（10μM）在注射6-OHDA后5天显着减少多巴胺能神经元。在多巴胺能神经元的再生过程中，头部区域的磷酸化组蛋白H3（H3P）阳性干细胞（称为“新生细胞”）增加；然而，MEK 抑制剂显着减少了 H3P 阳性新生细胞的数量。这些结果表明涡虫的多巴胺能神经元再生受到 MEK/ERK 通路的调节。
Planarian Dugesia japonica is a flatworm that can autonomously regenerate its own body after an artificial amputation. A recent report showed the role of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway in the head morphogenesis during the planarian regeneration process after amputation; however, neuron-specific regeneration mechanisms have not yet been reported. Here, whether MEK/ERK pathway was involved in the dopaminergic neuronal regeneration in planarians was investigated. Planarians regenerated their body within 14 days after amputation; however, the head region morphogenesis was inhibited by MEK inhibitor U0126 (3 or 10 mu M). Furthermore, the number of planarian tyrosine hydroxylase (DjTH)-positive dopaminergic neurons in the regenerated head region was also decreased by U0126. The 6-hydroxydopamine (6-OHDA), a dopaminergic neurotoxin, can decrease the number of dopaminergic neurons; however, planarians can regenerate dopaminergic neurons after injecting 6-OHDA into the intestinal tract. MEK inhibitor PD98059 (30 mu M) or U0126 (10 mu M) significantly decreased dopaminergic neurons 5 days after the 6-OHDA injection. During the regeneration process of dopaminergic neurons, phosphorylated histone H3 (H3P)-positive stem cells known as "neoblasts" were increased in the head region; however, MEK inhibitors significantly decreased the number of H3P-positive neoblasts. These results suggested that dopaminergic neuronal regeneration in planarian was regulated by the MEK/ERK pathway.