Comparative study on detectability of learning and memory disorder between two water maze tests commonly used in juvenile rat toxicity studies using isoflurane inhaled rat model.

IF 1.3 4区 医学 Q3 PEDIATRICS
Congenital Anomalies Pub Date : 2022-05-01 Epub Date: 2022-03-06 DOI:10.1111/cga.12460
Hiroshi Mineshima, Hiroki Kimoto, Masaya Hitomi, Fumika Akizawa, Yui Terayama, Tsuyoshi Yoshikawa
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引用次数: 0

Abstract

Evaluation of learning and memory is crucial in juvenile animal toxicity studies (JAS) during the development of CNS active drugs, but there are no currently recommended test methods. We compared the ability of the Morris water maze (MWM) and the Biel water maze (BWM) to detect learning and memory disorder (LMD) using rats inhaled isoflurane (IFN). Rats were treated with 1% IFN using inhalation on postnatal day (PND) 7 for 6 h. All rats were subjected to the MWM on PND 33 and the BWM on PND 55/57 (Experiment 1), or the BWM on PND 32/33 and the MWM on PND 54/55 (Experiment 2). On PND 70, the brain was weighed and then neurohistopathology was conducted. There were no IFN-related changes in clinical signs and body weight. In the tests beginning on PND 32/33, the MWM clearly detected IFN-related LMD in both sexes whereas the BWM detected LMD only in males. With an additional benefit of a simpler procedure, the MWM was considered superior to the BMW for JAS. LMD was not detected in both mazes tested from PND 54/55/57, which was considered due to weak effect and/or recovery of brain function with growth. Single IFN inhalation on PND 7 was considered useful as positive control to induce LMD caused by postnatal exposure in rats, but stronger treatment regimens was recommended.

异氟醚吸入大鼠幼年毒性研究中常用的两种水迷宫实验对学习记忆障碍可探测性的比较研究。
在开发中枢神经系统活性药物的过程中,学习和记忆的评估在幼年动物毒性研究(JAS)中至关重要,但目前没有推荐的测试方法。比较Morris水迷宫(MWM)和Biel水迷宫(BWM)对吸入异氟醚(IFN)大鼠学习记忆障碍(LMD)的检测能力。大鼠于出生后第7天(PND)吸入1% IFN治疗6小时。所有大鼠在PND 33上给予MWM并在PND 55/57上给予BWM(实验1),或在PND 32/33上给予BWM并在PND 54/55上给予MWM(实验2)。在PND 70上称重并进行神经组织病理学检查。临床症状和体重没有ifn相关的变化。在从PND 32/33开始的测试中,MWM在两性中都明显检测到ifn相关的LMD,而BWM仅在男性中检测到LMD。由于程序更简单,MWM被认为优于用于JAS的BMW。在PND 54/55/57测试的两个迷宫中均未检测到LMD,这可能是由于影响较弱和/或脑功能随生长而恢复。PND 7单次吸入IFN被认为是诱导大鼠出生后暴露引起的LMD的阳性对照,但建议使用更强的治疗方案。
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来源期刊
Congenital Anomalies
Congenital Anomalies PEDIATRICS-
自引率
0.00%
发文量
49
审稿时长
>12 weeks
期刊介绍: Congenital Anomalies is the official English language journal of the Japanese Teratology Society, and publishes original articles in laboratory as well as clinical research in all areas of abnormal development and related fields, from all over the world. Although contributions by members of the teratology societies affiliated with The International Federation of Teratology Societies are given priority, contributions from non-members are welcomed.
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