Mice with the deleted neurofilament of low‐molecular‐weight (Nefl) gene: 1. Effects on regional brain metabolism
Mice with the deleted neurofilament of low‐molecular‐weight (Nefl) gene: 1. Effects on regional brain metabolism
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DOI：
10.1002/jnr.20449
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发表时间：
2005-06
影响因子：
4.2
通讯作者：
M. Dubois;Robert Lalonde;J. Julien;C. Strazielle
中科院分区：
文献类型：
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作者：
M. Dubois;Robert Lalonde;J. Julien;C. Strazielle
神经元中间丝由与NFM和NFH连接的NFL亚基组成，它们的改变已被认为是运动神经元疾病的发病原因。小鼠中Nefl基因的耗尽模拟了肌萎缩侧索硬化症中所见的NFL mRNA水平降低，并导致神经丝蛋白的核周积累和运动神经元中的轴突萎缩。通过细胞色素氧化酶（考克斯）活性的定量组织化学估计来评估NFL -/-小鼠的局部脑代谢。NFL无效小鼠在许多后脑区域显示酶活性改变，主要是小脑、脑干的连接区域（红核、前庭核和网状结构）和脑神经核。所有受影响的地区提出升高的考克斯活性，除了小脑的浦肯野细胞和大细胞红核，酶活性较低。NFL-破坏的小鼠在肌萎缩侧索硬化症中受影响的脑干感觉运动区域中显示出功能改变。© 2005 Wiley利斯公司
Neuronal intermediate filaments consist of the NFL subunit linked with NFM and NFH, and their alterations have been proposed as a pathogenesic cause in motor neuron diseases. Depletion of the Nefl gene in mice mimicks the reduced NFL mRNA levels seen in amyotrophic lateral sclerosis and causes perikaryal accumulation of neurofilament proteins and axonal hypotrophy in motoneurons. NFL –/– mice were evaluated for regional brain metabolism by means of quantitative histochemical estimation of cytochrome oxidase (COx) activity. The NFL null mice displayed enzymatic activity alterations in numerous hindbrain regions, mainly the cerebellum, connected regions of the brainstem (red nucleus, vestibular nuclei, and reticular formation), and cranial nerve nuclei. All of the affected regions presented elevated COx activity, except for the Purkinje cells of the cerebellum and the magnocellular red nucleus, where enzymatic activity was lower. NFL‐disrupted mice displayed functional alterations in brainstem sensorimotor regions affected in amyotrophic lateral sclerosis. © 2005 Wiley‐Liss, Inc.