Wang Sensen, Zhuang Lei, Yang Xiaoxuan, Li Qiang, Xue Qingsheng, Luo Yan, Zhang Fujun, Yu Buwei
Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Neurosci Lett. 2015 Oct 21;607:114-119. doi: 10.1016/j.neulet.2015.09.022. Epub 2015 Sep 21.
Compared to neutral memory, emotional memory is extremely strong and persistent immediately after acquisition, therefore it may recruit specific mechanisms during acquisition. The calcineurin-dependent mechanisms engaging early growth response 1 (Egr-1) have been proved to determine the strength of emotional memory during establishment. Isoflurane, a widely used inhalation anesthetic, can interfere with the acquisition of emotional memory. We hypothesized that isoflurane impairs the acquisition of conditioned taste aversion (CTA) memory in rats and the Egr-1 expression regulation via calcineurin (CaN) and ERK signaling pathway is involved in isoflurane-induced repression of CTA memory. To examine this, we investigated the influence of isoflurane on CTA memory and the expression and activity of CaN, the phosphorylation level of ERK and the expression of Egr-1 in amygdala in response to CTA training in rats. The results showed that isoflurane exposure (1.5%, 2h) before training impaired the acquisition of CTA memory in rats. Isoflurane exposure increased the CaN activity and decreased the p-ERK and Egr-1 in amygdala in rats. These findings suggest that isoflurane can disrupt the establishment of aversion memory, and CaN activation associating with p-ERK and Egr-1 down-regulation may contribute to the isoflurane induced impairment of aversion memory acquisition.
与中性记忆相比，情绪记忆在形成后立即表现出极强的强度和持久性，因此在形成过程中可能会调用特定机制。已证实钙调神经磷酸酶依赖性机制通过早期生长反应因子1（Egr-1）来决定情绪记忆形成过程中的强度。异氟烷，一种广泛使用的吸入性麻醉剂，能够干扰情绪记忆的形成。我们假设异氟烷会损害大鼠条件性味觉厌恶（CTA）记忆的形成，并且通过钙调神经磷酸酶（CaN）和细胞外信号调节激酶（ERK）信号通路对Egr-1表达的调控参与了异氟烷诱导的CTA记忆抑制。为了验证这一点，我们研究了异氟烷对大鼠CTA记忆以及杏仁核中CaN的表达和活性、ERK的磷酸化水平和Egr-1表达的影响，这些影响是大鼠对CTA训练的反应。结果显示，训练前暴露于异氟烷（1.5%，2小时）会损害大鼠CTA记忆的形成。异氟烷暴露会增加大鼠杏仁核中CaN的活性，并降低p-ERK和Egr-1的水平。这些发现表明，异氟烷能够破坏厌恶记忆的形成，并且CaN的激活与p-ERK和Egr-1的下调可能共同导致了异氟烷诱导的厌恶记忆形成受损。
