Hyperactivity and hypoactivity in a rat model of Huntington's disease: the systemic 3-nitropropionic acid model

Hyperactivity and hypoactivity in a rat model of Huntington's disease: the systemic 3-nitropropionic acid model
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DOI:
10.1016/s1385-299x(96)00037-2
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发表时间:
1997-08-01
期刊:
BRAIN RESEARCH PROTOCOLS
影响因子:
--
通讯作者:
Sanberg, PR
Sanberg, PR
中科院分区:
其他
文献类型:
--
作者:
Borlongan, CV;Koutouzis, TK;Sanberg, PR

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本研究建议使用全身 3-硝基丙酸 (3-NP) 治疗大鼠作为亨廷顿病 (HD) 模型。全身 3-NP 模型涉及在一段时间内每 4 天向大鼠慢性腹膜内 (i.p.) 注射一次低剂量 3-NP。我们的实验研究证据表明,控制注射次数可能会导致夜间自发运动活动增加(多动)或夜间运动不能(活动减退)[1]。例如,注射两次3-NP(采用每4天注射一次的治疗)会导致活动过度,而注射四次或更多3-NP会导致活动减退1:1]。运动活动由 Digiscan 运动活动监视器记录 [11]。对这两种类型的运动活动的观察是独特的,因为没有兴奋毒素模型能够复制 HD 样行为改变的两阶段进展。大多数使用喹啉酸 (QA) 和红藻氨酸 (KA) 等兴奋性毒素的研究仅再现了多动阶段 [4,5,7]。利用系统性 3-NP 模型,可以对疾病的至少两个阶段进行研究。这可以更好地评估干预策略,例如疾病不同阶段的神经移植。全身性3-NP大鼠模型被认为是HD动物模型的改进。 (C) 1997 Elsevier Science B.V.
The present study proposes the use of systemic 3-nitropropionic acid (3-NP) treatment in rats as a model of Huntington's disease (HD). The systemic 3-NP model involves chronic injection of low dose intraperitoneal (i.p.) injections of 3-NP to rats once every 4 days over a period of time. Evidence from our experimental studies suggests that manipulating the number of injections can result in either increased nocturnal spontaneous locomotor activity (hyperactivity) or nocturnal akinesia (hypoactivity) [1]. For example, two injections of 3-NP (using the treatment of one injection every 4 days) result in hyperactivity, while four injections or more of 3-NP lead to hypoactivity 1:1]. The locomotor activity is recorded by Digiscan locomotor activity monitors [11]. The observation of these two types of locomotor activity is unique since no excitotoxin model has replicated a two-stage progression of a HD-like behavioral alteration. Most studies using excitotoxins like quinolinic acid (QA) and kainic acid (KA) have only reproduced the hyperactivity stage [4,5,7]. With the systemic 3-NP model, investigations into at least two stages of the disease are made possible. This allows for better assessment of intervention strategies such as neural transplants across different stages of the disease. The systemic 3-NP rat model is believed to be an improved animal model of HD. (C) 1997 Elsevier Science B.V.