Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation
Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation
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DOI：
10.1016/j.brainres.2004.07.030
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发表时间：
2004-10-15
期刊：
影响因子：
2.9
通讯作者：
Cooper, JD
中科院分区：
文献类型：
--
作者：
Pontikis, CC;Cella, CV;Cooper, JD
神经元蜡样质脂褐质沉积症（NCL）的小鼠模型表现出人类疾病的许多特征，在海马和新皮质中具有广泛的区域萎缩和GABA能中间神经元的显著损失。反应性神经胶质增生是所有形式的NCL的特征，但尚不清楚神经胶质活化是否先于神经元损失或由神经元损失触发。为了探讨这个问题，我们进行了详细的形态学表征的Cln 3无效突变（Cln（-/-））小鼠模型的青少年NCL（JNCL），揭示了一个迟发性神经退行性表型，没有显着的区域萎缩，但广泛的损失海马中间神经元，这是第一次明显的年龄在14个月。定量图像分析表明，在5个月大的症状前Cln 3（-/-）小鼠中，星形胶质细胞和小胶质细胞活化标志物的上调，在显著的神经元损失发生前数月。这些数据为JNCL发病机制早期的细微胶质反应提供了证据。(C)2004 Elsevier B. V.保留所有权利。
Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis. (C) 2004 Elsevier B.V. All rights reserved.