Alaverdashvili Mariam, Lapointe Valerie, Whishaw Ian Q, Cross Albert R
Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Magn Reson Insights. 2017 May 3;10:1178623X17706878. doi: 10.1177/1178623X17706878. eCollection 2017.
Manganese-enhanced magnetic resonance imaging (MEMRI) has been suggested to be a useful tool to visualize and map behavior-relevant neural populations at large scale in freely behaving rodents. A primary concern in MEMRI applications is Mn toxicity. Although a few studies have specifically examined toxicity on gross motor behavior, Mn toxicity on skilled motor behavior was not explored. Thus, the objective of this study was to combine manganese as a functional contrast agent with comprehensive behavior evaluation. We evaluated Mn effect on skilled reach-to-eat action, locomotion, and balance using a single pellet reaching task, activity cage, and cylinder test, respectively. The tests used are sensitive to the pathophysiology of many neurological and neurodegenerative disorders of the motor system. The behavioral testing was done in combination with a moderate dose of manganese. Behavior was studied before and after a single, intravenous infusion of MnCl (48 mg/kg). The rats were imaged at 1, 3, 5, 7, and 14 days following infusion. The results show that MnCl infusion resulted in detectable abnormalities in skilled reaching, locomotion, and balance that recovered within 3 days compared with the infusion of saline. Because some tests and behavioral measures could not detect motor abnormalities of skilled movements, comprehensive evaluation of motor behavior is critical in assessing the effects of MnCl. The relaxation mapping results suggest that the transport of Mn into the brain is through the choroid plexus-cerebrospinal fluid system with the primary entry point and highest relaxation rates found in the pituitary gland. Relaxation rates in the pituitary gland correlated with measures of motor skill, suggesting that altered motor ability is related to the level of Mn circulating in the brain. Thus, combined MEMRI and behavioral studies that both achieve adequate image enhancement and are also free of motor skills deficits are difficult to achieve using a single systemic dose of MnCl.
锰增强磁共振成像（MEMRI）已被认为是一种有用的工具，可在自由活动的啮齿动物中大规模可视化和绘制与行为相关的神经群体。MEMRI应用中的一个主要问题是锰毒性。尽管有一些研究专门研究了锰对总体运动行为的毒性，但尚未探讨锰对熟练运动行为的毒性。因此，本研究的目的是将锰作为一种功能造影剂与全面的行为评估相结合。我们分别使用单颗粒抓取任务、活动笼和圆筒试验评估了锰对熟练的进食抓取动作、运动和平衡的影响。所使用的测试对运动系统的许多神经和神经退行性疾病的病理生理学敏感。行为测试是在中等剂量的锰的情况下进行的。在单次静脉注射MnCl（48mg/kg）之前和之后研究行为。在注射后1、3、5、7和14天对大鼠进行成像。结果表明，与注射生理盐水相比，注射MnCl导致熟练抓取、运动和平衡方面出现可检测到的异常，这些异常在3天内恢复。由于一些测试和行为测量无法检测到熟练运动的运动异常，因此在评估MnCl的影响时，对运动行为进行全面评估至关重要。弛豫映射结果表明，锰进入大脑的运输是通过脉络丛 - 脑脊液系统，垂体是主要的进入点且弛豫率最高。垂体中的弛豫率与运动技能的测量相关，表明运动能力的改变与大脑中循环的锰水平有关。因此，使用单次全身剂量的MnCl很难同时实现足够的图像增强且不存在运动技能缺陷的MEMRI和行为研究。
