Intracranial self-stimulation-reward or immobilization-aversion had different effects on neurite extension and the ERK pathway in neurotransmitter-sensitive mutant PC12 cells
Intracranial self-stimulation-reward or immobilization-aversion had different effects on neurite extension and the ERK pathway in neurotransmitter-sensitive mutant PC12 cells
复制标题
颅内自我刺激奖励或固定厌恶对神经递质敏感突变PC12细胞中的神经突延伸和ERK通路有不同的影响
DOI：
10.1016/j.bbr.2020.112920
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发表时间：
2021
影响因子：
2.7
通讯作者：
Kano Yoshio
中科院分区：
文献类型：
--
作者：
Gomita Yutaka;Esumi Satoru;Ushio Soichiro;Kitamura Yoshihisa;Sendo Toshiaki;Motoda Hirotoshi;Inoue Shigeki;Araki Hiroaki;Kano Yoshio
各种行为都会引发愉悦（奖励）或厌恶（惩罚）作为情绪反应。长期对大脑神经控制过程产生负面影响的情绪因素可能会诱发神经元变化，从而导致各种精神疾病。在本研究中，使用了新开发的 PC12m12 细胞，该细胞对乙酰胆碱 (ACh) 等神经递质高度敏感。将细胞暴露于经过颅内自刺激（ICSS）的大鼠血浆中，神经突生长显着上调。此外，自愿在轮子上奔跑或强迫在旋转杆上奔跑被用来诱导大鼠的行为兴奋，并且对其血浆的检查证实ICSS诱导的神经突生长与ICSS行为本身无关。此外，免疫印迹和 U0126（一种 ERK（细胞外信号调节激酶）拮抗剂）治疗表明，ICSS 诱导的神经突生长与神经元 ERK 活性相关。将相同的细胞暴露于来自已进行固定化（IMM）的大鼠的血浆中也增加了神经突的生长。虽然增强程度不如ICSS大鼠血浆处理后观察到的那么大，但仍低于用ACh作为阳性对照处理后观察到的增强程度。这些结果表明，ICSS 或 IMM 导致 PC12m12 细胞中不同程度的形态变化，例如神经突生长增强，但这些效应背后的神经元信号转导途径不同；也就是说，前者的形态变化可能涉及ERK通路的激活，而后者的变化可能不会。利用对神经递质表现出敏感性的PC12m12细胞，有可能在神经元水平上阐明精神疾病的发病机制并寻找治疗药物。
Various actions trigger pleasure (reward) or aversion (punishment) as emotional responses. Emotional factors that negatively affect brain neural control processes for long periods of time might cause various mental diseases by inducing neuronal changes. In the present study, newly developed PC12m12 cells which are highly sensitivity to neurotransmitters such as acetylcholine (ACh), were used. Exposing the cells to plasma from rats that had been subjected to intracranial self-stimulation (ICSS) markedly upregulated neurite outgrowth. In addition, voluntary running in a wheel or forced on a rotating rod was used to induce behavioral excitation in rats, and examinations of their plasma confirmed that the ICSS-induced neurite outgrowth was not associated with the ICSS behavior itself. Furthermore, immunoblotting and treatment with U0126, an ERK (extracellular signal-regulated kinase) antagonist, showed that the ICSS-induced neurite outgrowth was related to neuronal ERK activity. Exposing the same cells to plasma from rats that had been subjected to immobilization (IMM) also increased neurite outgrowth. Although the degree of enhancement was not as great as that seen after the ICSS rat plasma treatment, it was less than that observed after treatment with ACh as a positive control. These results indicate that ICSS or IMM lead to varying degrees of morphological changes, such as enhanced neurite outgrowth, in PC12m12 cells, but the neuronal signal transduction pathways underlying these effects differ; i.e.,the former morphological change might involve the activation of the ERK pathway, whereas the latter changes might not. Using PC12m12 cells which exhibit sensitivity to neurotransmitters, it might be possible to clarify the pathogeneses of mental diseases at the neuronal level and search for therapeutic drugs.