Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice
Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice
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DOI：
10.1016/j.bbr.2008.03.024
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发表时间：
2008-08-05
影响因子：
2.7
通讯作者：
Hemsley, Kim M.
中科院分区：
文献类型：
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作者：
Lau, Adeline A.;Crawley, Allison C.;Hemsley, Kim M.
粘多糖病（MPS） IIIA，或Sanfilippo综合征，是一种溶酶体积存障碍，其特征是严重和进行性神经病理。在无症状期后，患者可能出现睡眠障碍、认知能力下降、攻击倾向和多动。自然产生的MPS IIIA小鼠模型也表现出许多这些行为特征，并且最近被回交到C57BL/6遗传背景上。为了更彻底地表征基因MPS IIIA小鼠的行为表型，我们评估了在高程迷宫（EPM）和开阔场地运动活动中的探索活动和无条件焦虑相关行为。尽管MPS IIIA雄性小鼠在18周龄和20周龄时EPM的活跃程度较低，但它们比正常小鼠更有可能探索张开的双臂，这表明它们的焦虑程度有所降低。反复的EPM测试减少了MPS IIIA小鼠对张开的手臂的探索。在野外试验中，从10周龄开始，未经试验的雄性MPS IIIA小鼠的活动明显减少。雌性正常小鼠和MPS IIIA小鼠在野外试验中表现出相似的探索性活动。这些焦虑和运动活动的差异将使我们能够评估MPS IIIA治疗方案的有效性，作为开发安全有效的Sanfilippo患者治疗方法的先导。爱思唯尔B.V.版权所有
Mucopolysaccharidosis (MPS) IIIA, or Sanfilippo syndrome, is a lysosomal storage disorder characterized by severe and progressive neuropathology. Following an asymptomatic period, patients may present with sleep disturbances, cognitive decline, aggressive tendencies and hyperactivity. A naturally-occurring mouse model of MPS IIIA also exhibits many of these behavioral features and has been recently back-crossed onto a C57BL/6 genetic background. To more thoroughly characterize the behavioral phenotype of congenic MPS IIIA mice, we assessed exploratory activity and unconditioned anxiety-related behavior in the elevated plus maze (EPM) and open field locomotor activity. Although MPS IIIA male mice were less active in the EPM at 18 and 20 weeks of age, they were more likely to explore the open arms than their normal counter-parts suggesting reduced anxiety. Repeated EPM testing reduced exploration of the open arms in MPS IIIA mice. In the open field test, significant reductions in activity were evident in naive-tested male MPS IIIA mice from 10 weeks of age. Female normal and MPS IIIA mice displayed similar exploratory activity in the open field test. These differences in anxiety and locomotor activity will allow us to evaluate the efficacy of therapeutic regimes for MPS IIIA as a forerunner to developing safe and effective therapies for Sanfilippo patients. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.