丙泊酚麻醉和非厌恶记忆提取以及青春期大鼠腹侧海马体中参与记忆过程的分子的表达
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Propofol anesthesia exposure and nonaversive memory retrieval and the expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats
背景与目的：麻醉药物对儿童术后认知功能的影响并没有很明确的结论，也没有用实验证实。本研究的目的是探讨丙泊酚麻醉对腹侧海马体中海马相关的非厌恶学习和参与记忆过程的生物化学变化的影响，青春期大鼠作为青少年的啮齿动物模型。
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方法：利用短期空间适应和新物体识别测试，对空间和非空间、非厌恶的海马相关的学习进行评估。在这两项测试中，在同等可比较的长期学习之后进行麻醉。行为测试持续2天。在行为测试的时候，通过蛋白质免疫印迹和免疫组织化学，研究了腹侧海马体中记忆提取/再巩固中涉及到的分子表达的变化。
结果：在测试开始时，丙泊酚麻醉会导致对新环境的不适当评估，并且会影响在空间适应测试中继续进行的研究。在测试开始的时候，这种处理并不会影响到对新物体的识别，但是它减弱了对新事物的整体偏好，反映了对薄弱记忆的提取。磷酸化的细胞外信号调节激酶2（涉及到记忆提取）的表达减少了，而在腹侧海马体中磷酸化Ca2+/钙调蛋白依赖蛋白激酶IIa和早期生长反应蛋白1（涉及到记忆再巩固）增加了。在背齿状回， Finkel-Biskis-Jinkins小鼠骨肉瘤病毒同型致癌基因B（神经元活动指标）的水平提高了。处理后48小时，丙泊酚麻醉（PAE）组在两种测试中探索性活动增强明显。
结论：丙泊酚麻醉会影响青春期大鼠记忆提取和在处理后24小时内的空间和非空间的、非厌恶学习，以及在腹侧海马体中参与记忆提取/再巩固的分子的表达。这些结果可能具有临床意义，在丙泊酚麻醉后，有利于控制年龄较大的儿童的基本认知功能。
Pavković Ž1, Milanović D1, Ruždijić S1, Kanazir S1, Pešić V1.
Propofol anesthesia exposure and nonaversive memory retrieval and the expression ofmolecules involved in memory process in the dorsal hippocampus in peripubertal rats.
Paediatr Anaesth. May 12，2018 . doi: 10.1111/pan.13396. [Epub ahead of print]
BACKGROUND:The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed.
Aims: The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus-dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence.
METHODS:The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus-dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24-hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing.
RESULTS:Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal-regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca2+/calmodulin-dependent protein kinase IIa and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks.
CONCLUSIONS:In peripubertal rats, propofol anesthesia exposure affects memory retrieval and acquisition of new le arning in the spatial and nonspatial, nonaversive learning tasks 24 hour after the treatment, along with the expression of molecules that participate in memory retrieval/reconsolidation in the dorsal hippocampus. These results may have clinical implications, favoring control of basic cognitive functions in older children after the propofol exposure.
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