Oxidative Stress and Autophagic Alteration in Brainstem of SOD1-G93A Mouse Model of ALS

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• 作者：Ting An (1) (5)
  Pengxiao Shi (1)
  Weisong Duan (1) (2) (3)
  Shipan Zhang (1)
  Pin Yuan (1)
  Zhongyao Li (1) (2)
  Dongxia Wu (1) (2)
  Zuoshang Xu (4)
  Chunyan Li (1) (2) (3)
  Yansu Guo (1) (2) (3)
  
• 关键词：Amyotrophic lateral sclerosis ; Transgenic mice ; Brainstem ; Motor nucleus ; Autophagy ; Oxidative stress
• 刊名：Molecular Neurobiology
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：49
• 期：3
• 页码：1435-1448
• 全文大小：
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• 作者单位：Ting An (1) (5)
  Pengxiao Shi (1)
  Weisong Duan (1) (2) (3)
  Shipan Zhang (1)
  Pin Yuan (1)
  Zhongyao Li (1) (2)
  Dongxia Wu (1) (2)
  Zuoshang Xu (4)
  Chunyan Li (1) (2) (3)
  Yansu Guo (1) (2) (3)
  
  1. Department of Neurology, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, Hebei Province, 050000, China
  5. Department of Neurology, Beijing Shunyi Hospital of China Medical University, Beijing, 101300, China
  2. Key Laboratory of Hebei Neurology, Shijiazhuang, Hebei, 050000, China
  3. Institute of Cardiocerebrovascular Disease, Shijiazhuang, Hebei, 050000, China
  4. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA
  
• ISSN：1559-1182

文摘

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease involving both upper and lower motor neurons. The mechanism of motor neuron degeneration is still unknown. Although many studies have been performed on spinal motor neurons, few have been reported on brainstem and its motor nuclei. The aim of this study was to investigate oxidative stress and autophagic changes in the brainstem and representative motor nuclei of superoxide dismutase 1 (SOD1)-G93A mouse model of ALS. The expression levels of cluster of differentiation molecule 11b (CD11b), glial fibrillary acidic protein, glutamate–cysteine ligase catalytic subunit, heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, voltage-dependent anion-selective channel protein 1, Sequestosome 1/p62 (p62), microtubule-associated protein 1 light chain 3B (LC3), and SOD1 proteins in brainstem were examined by Western blot analysis. Immunohistochemistry and immunofluorescence were performed to identify the cellular localization of SOD1, p62, and LC3B, respectively. The results showed that there were progressive asctrocytic proliferation and microglial activation, induction of antioxidant proteins, and increased p62 and LC3II expression in brainstem of SOD1-G93A mice. Additionally, SOD1 and p62 accumulated in hypoglossal, facial, and red nuclei, but not in oculomotor nucleus. Furthermore, electron microscope showed increased autophagic vacuoles in affected brainstem motor nuclei. Our results indicate that brainstem share similar gliosis, oxidative stress, and autophagic changes as the spinal cord in SOD1-G93A mice. Thus, SOD1 accumulation in astrocytes and neurons, oxidative stress, and altered autophagy are involved in motor neuron degeneration in the brainstem, similar to the motor neurons in spinal cord. Therefore, therapeutic trials in the SOD1G93A mice need to target the brainstem in addition to the spinal cord.