Development of motor deficits in a murine model of mucopolysaccharidosis type IIIA (MPS-IIIA)
Development of motor deficits in a murine model of mucopolysaccharidosis type IIIA (MPS-IIIA)
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DOI：
10.1016/j.bbr.2004.08.019
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发表时间：
2005-03-30
影响因子：
2.7
通讯作者：
Hopwood, JJ
中科院分区：
文献类型：
--
作者：
Hemsley, KM;Hopwood, JJ
粘多糖沉积症（NIPS）IIIA型或Sanfilippo综合征是一种以进行性神经病理学为特征的溶酶体储存障碍。患者表现出攻击性、睡眠紊乱、多动和智力下降，最终导致营养不良和死亡。最近，人们发现了MPS-IIIA小鼠模型，其临床体征和神经病理变化都与人类疾病相似。这为我们提供了一个机会来研究这种疾病的病理进展，并确定新疗法的疗效，因为目前所有影响大脑的溶酶体贮积症（LSD）都是无法治疗的。神经病理学变化先前已被描述在涉及调节运动功能的大脑区域中，因此，在本研究中，我们试图确定MPS-IIIA小鼠中是否存在可量化的运动异常，如果存在，则在什么年龄时它们变得可检测。对3 - 40周龄的MPS-IIIA和正常雄性和雌性小鼠进行旷场运动活动、后肢步态、僵住症、神经肌肉强度和负趋地性测试。在MPS-IIIA小鼠中，从3周开始观察到旷场活动的显著变化，而在步态、握力测试和负趋地性反应评估中的异常从相似至15周龄开始观察到。在雄性MPS-IIIA小鼠中经常检测到行为变化，然后才出现在雌性小鼠中。我们的观察提供了对MPS-IIIA脑内病理变化的时间顺序的洞察，并且这一简单的系列测试将证明在对这种情况进行实验性治疗后的小鼠进行比较时是有用的。(C)2004 Elsevier B. V.保留所有权利。
Mucopolysaccharidosis (NIPS) type IIIA or Sanfilippo syndrome is a lysosomal storage disorder characterised by progressive neurological pathology. Patients exhibit aggression, disturbed sleep, hyperactivity and mental decline ultimately resulting in inanition and death. Recently, a mouse model of MPS-IIIA was discovered, and both the clinical signs and neuropathological changes mimic the human disease. This provides us with an opportunity to study the pathological progression of this disorder and to determine the efficacy of novel therapies, for at present all lysosomal storage disorders (LSD) affecting the brain are untreatable. Neuropathological changes have previously been described in areas of the brain involved in regulating motor function, therefore, in the present study we sought to determine whether quantifiable motor abnormalities were present in the MPS-IIIA mouse, and if so, at what age they became detectable. Tests of open-field locomotor activity, hindlimb gait, catalepsy, neuromuscular strength and negative geotaxis were administered to MPS-IIIA and normal male and female mice aged from 3 to 40 weeks of age. Significant changes in open-field activity were observed from 3 weeks in MPS-IIIA mice, whereas abnormalities in tests of gait, grip strength and in the assessment of the negative geotaxis response were observable from similar to15 weeks of age. Behavioural changes were often detected in male MPS-IIIA mice before they appeared in females. Our observations provide insight into the chronology of pathological changes within the MPS-IIIA brain and this simple series of tests will prove useful in comparing mice following the administration of experimental therapies for this condition. (C) 2004 Elsevier B.V. All rights reserved.