Centre for Cognitive and Neural Systems (CCNS), School of Biomedical Sciences, University of Edinburgh, Edinburgh, UK.
Behav Brain Res. 2011 Jan 1;216(1):293-300. doi: 10.1016/j.bbr.2010.08.007. Epub 2010 Aug 14.
Manganese (Mn(2+))-enhanced magnetic resonance (MR) imaging (MEMRI) in rodents offers unique opportunities for the longitudinal study of hippocampal structure and function in parallel with cognitive testing. However, Mn(2+) is a potent toxin and there is evidence that it can interfere with neuronal function. Thus, apart from causing adverse peripheral side effects, Mn(2+) may disrupt the function of brain areas where it accumulates to produce signal enhancement and, thereby, Mn(2+) administration may confound cognitive testing. Here, we examined in male adult Lister hooded rats if a moderate systemic dose of MnCl₂ (200 μmol/kg; two intraperitoneal injections of 100 μmol/kg separated by 1 h) that produces hippocampal MR signal enhancement would disrupt hippocampal function. To this end, we used a delayed-matching-to-place (DMP) watermaze task, which requires rapid allocentric place learning and is highly sensitive to interference with hippocampal function. Tested on the DMP task 1 h and 24 h after MnCl₂ injection, rats did not show any impairment in indices of memory performance (latencies, search preference) or any sensorimotor effects. However, MnCl₂ injection caused acute peripheral effects (severe ataxia and erythema, i.e. redness of paws, ears, and nose) which subsided over 30 min. Additionally, rats injected with MnCl₂ showed reduced weight 1 day after injection and failed to reach the normal weight-growth curve of control rats within the 16 days monitored. Our results indicate that 200 μmol/kg MnCl₂ produces hippocampal MR signal enhancement without disrupting hippocampus-dependent behavior on a rapid place learning task, even though attention must be paid to peripheral side effects.
锰（Mn(2+)）增强磁共振（MR）成像（MEMRI）在啮齿动物中提供了独特的机会，可以在进行认知测试的同时对海马体结构和功能进行纵向研究。然而，Mn(2+)是一种有效的毒素，有证据表明它会干扰神经元功能。因此，除了引起不良的外周副作用外，Mn(2+)可能会破坏其积累的脑区的功能，从而产生信号增强，并且，Mn(2+)的给药可能会混淆认知测试。在这里，我们在雄性成年 Lister Hooded 大鼠中检查了中等剂量的 MnCl₂（200 μmol/kg；两次腹腔注射 100 μmol/kg，间隔 1 小时）是否会破坏海马体功能，该剂量会导致海马体的 MR 信号增强。为此，我们使用了延迟匹配到位置（DMP）水迷宫任务，该任务需要快速进行位置学习，并且对海马体功能的干扰非常敏感。在 MnCl₂注射后 1 小时和 24 小时测试 DMP 任务时，大鼠的记忆表现（潜伏期、搜索偏好）指数或任何感觉运动效应均未受损。然而，MnCl₂注射会引起急性外周效应（严重的共济失调和红斑，即爪子、耳朵和鼻子发红），这些效应在 30 分钟内消退。此外，MnCl₂注射的大鼠在注射后 1 天体重减轻，并且在 16 天的监测期间未能达到对照大鼠的正常体重增长曲线。我们的结果表明，200 μmol/kg MnCl₂在快速位置学习任务中产生海马体 MR 信号增强而不会破坏海马体依赖性行为，尽管必须注意外周副作用。
