Age-dependent cognitive decline and amygdala pathology in α-synuclein transgenic mice
Age-dependent cognitive decline and amygdala pathology in α-synuclein transgenic mice
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DOI：
10.1016/j.neurobiolaging.2006.06.013
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发表时间：
2007-09-01
影响因子：
4.2
通讯作者：
Kahle, Philipp J.
中科院分区：
文献类型：
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作者：
Freichel, Christian;Neumann, Manuela;Kahle, Philipp J.
神经元内α -突触核蛋白（aSYN）包涵体是许多神经退行性疾病的标志性病变，包括帕金森病和路易体痴呆。在泛神经元Thy I启动子控制下表达突变体[A30P]（α SYN）的转基因小鼠模型中，运动障碍在17月龄后变得明显。在Morris水迷宫和恐惧条件反射中测量认知表现。在4个月大时，转基因小鼠的表现与对照组相似。然而，12个月大的(Thy 1)-h[A30P] α SYN小鼠在这些任务中的表现明显受损。认知测试结束后，处死小鼠，观察神经病理的区域分布。与4个月大的动物相比，12个月大的转基因小鼠在大脑的几个区域表现出α -突触核蛋白病，包括杏仁核中央核，这与小鼠的认知行为有关，并且容易发生人类患者的aSYN病理。因此，在转基因小鼠模型中，伴随认知能力下降的特定皮质区域aSYN的年龄依赖性纤维化可能反映了路易体痴呆。(C) 2006爱思唯尔公司版权所有。
Intraneuronal alpha-synuclein (aSYN) inclusions constitute the hallmark lesions of a number of neurodegenerative diseases, including Parkinson's disease and dementia with Lewy bodies. In a transgenic mouse model expressing mutant [A30P](alpha SYN under control of the pan-neuronal Thy I promoter, motor impairment became significant beyond 17 months of age. Cognitive performance was measured in the Morris water maze and upon fear conditioning. At 4 months of age, transgenic mice performed like controls. However, performance in these tasks was significantly impaired in (Thy 1)-h[A30P]alpha SYN mice at 12 months of age. After completion of the cognition tests, mice were sacrificed and the regional distribution of neuropathology was examined. In contrast to 4 months old animals, 12 months old transgenic mice showed alpha-synucleinopathy in several brain regions, including the central nucleus of the amygdala, which is involved in cognitive behavior of mice, and is susceptible to aSYN pathology in human patients. Thus, age-dependent fibrillization of aSYN in specific cortical regions concomitant with cognitive decline may reflect dementia with Lewy bodies in a transgenic mouse model. (C) 2006 Elsevier Inc. All rights reserved.