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首页> 外文期刊>The European Journal of Neuroscience >Non-motor behavioural impairments in parkin-deficient mice.
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Non-motor behavioural impairments in parkin-deficient mice.

机译：帕金缺乏症小鼠的非运动行为障碍。

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Mutations in the parkin gene are the major cause of early-onset familial Parkinson's disease (PD). We previously reported the generation and analysis of a knockout mouse carrying a deletion of exon 3 in the parkin gene. F1 hybrid pa+/- mice were backcrossed to wild-type C57Bl/6 for three more generations to establish a pa-/-(F4) mouse line. The appearance of tyrosine hydroxylase-positive neurons was normal in young and aged pa-/- (F4) animals. Loss of parkin function in mice did not enhance vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity. However, the pa-/- (F4) mice displayed impaired exploration and habituation to a new environment and exhibited thigmotaxis behaviour in the open field and Morris water maze. Abnormal anxiety-related behaviour of pa-/- (F4) mice was also observed in the light/dark exploration test paradigm. Dopamine metabolism was enhanced in the striatum of pa-/- (F4) mice, as revealed by increased homovanillic acid (HVA) content and a reduced ratio of dihydroxyphenylacetic acid (DOPAC)/HVA. The alterations found in the dopaminergic system could be responsible for the behavioural impairments of pa-/- (F4) mice. Consistent with a recent observation of cognitive dysfunction in parkin-linked patients with PD, our findings provide evidence of a physiological role of parkin in non-motor behaviour, possibly representing a disease stage that precedes dopaminergic neuron loss.
机译：帕金基因的突变是早发家族性帕金森氏病（PD）的主要原因。我们先前曾报道了在Parkin基因中携带外显子3缺失的基因敲除小鼠的产生和分析。将F1杂种pa +/-小鼠与野生型C57Bl / 6回交三代，以建立pa-/-（F4）小鼠品系。幼年和老年pa-/-（F4）动物中酪氨酸羟化酶阳性神经元的外观正常。小鼠的帕金蛋白功能丧失并未增强多巴胺能神经元对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）毒性的脆弱性。但是，pa-/-（F4）小鼠对新环境的探索和适应能力受损，并且在开阔田野和莫里斯水迷宫中表现出趋轴行为。在亮/暗探索测试范例中也观察到了PA-/-（F4）小鼠异常的焦虑相关行为。多酚胺代谢在pa-/-（F4）小鼠的纹状体中得到增强，这通过高香草酸（HVA）含量的增加和二羟基苯基乙酸（DOPAC）/ HVA比例的降低来揭示。在多巴胺能系统中发现的改变可能是pa-/-（F4）小鼠行为受损的原因。与最近在帕金相关的PD患者中认知功能障碍的观察结果一致，我们的发现提供了帕金在非运动行为中的生理作用的证据，可能代表了多巴胺能神经元丧失之前的疾病阶段。

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