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Manganese-Enhanced Magnetic Resonance Imaging and Studies of Rat Behavior: Transient Motor Deficit in Skilled Reaching, Rears, and Activity in Rats After a Single Dose of MnCl

机译:锰增强磁共振成像和大鼠行为研究:单剂MnCl给药后大鼠短暂伸手,后方和活动中的短暂运动障碍

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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 Mn2+ toxicity. Although a few studies have specifically examined toxicity on gross motor behavior, Mn2+ 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 Mn2+ 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 MnCl2 (48 mg/kg). The rats were imaged at 1, 3, 5, 7, and 14 days following infusion. The results show that MnCl2 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 MnCl2. The relaxation mapping results suggest that the transport of Mn2+ 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 MnCl2.
机译:锰增强磁共振成像(MEMRI)被认为是在行为自由的啮齿动物中大规模可视化和绘制与行为相关的神经种群的有用工具。 MEMRI应用中的主要关注点是Mn2 +毒性。尽管一些研究专门研究了对总体运动行为的毒性,但尚未探索Mn2 +对熟练运动行为的毒性。因此,本研究的目的是将锰作为功能性造影剂与综合行为评估相结合。我们分别使用单个颗粒到达任务,活动笼和气瓶测试评估了Mn2 +对熟练的进食动作,运动和平衡的影响。所使用的测试对运动系统的许多神经系统疾病和神经退行性疾病的病理生理敏感。结合中等剂量的锰进行行为测试。在单次静脉内注射MnCl2(48 mg / kg)之前和之后研究行为。输注后第1、3、5、7和14天对大鼠成像。结果表明,与注入生理盐水相比,MnCl2注入导致可检测的异常触觉,运动和平衡异常,并在3天内恢复。由于某些测试和行为措施无法检测熟练运动的运动异常,因此,对运动行为进行全面评估对于评估MnCl2的影响至关重要。弛豫作图结果表明,Mn2 +进入大脑的途径是通过脉络丛-脑脊液系统,其主要进入点是垂体,其弛豫率最高。垂体的放松率与运动技能的测量值相关,表明运动能力的改变与大脑中锰的循环水平有关。因此,使用单一全身剂量的MnCl2既难以获得足够的图像增强效果又没有运动技能缺陷的联合MEMRI和行为研究。

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