中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (11): 1988-1994.doi: 10.4103/1673-5374.239447

• 原著:退行性病与再生 • 上一篇    下一篇

富集环境能提高SAMP8小鼠大脑黑质中生长相关蛋白43的表达

  

  • 收稿日期:2018-06-21 出版日期:2018-11-15 发布日期:2018-11-15
  • 基金资助:

    河北省卫生厅基金项目（20120056,20140314），河北省引进人才项目（C2011003039）

Enriched environment elevates expression of growth associated protein-43 in the substantia nigra of SAMP8 mice

Zhen-Yun Yuan, Jie Yang, Xiao-Wei Ma, Yan-Yong Wang, Ming-Wei Wang   

  1. The First Hospital of Hebei Medical University; Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province, Shijiazhuang, Hebei Province, China
  • Received:2018-06-21 Online:2018-11-15 Published:2018-11-15
  • Contact: Zhen-Yun Yuan, MD, PhD, yuanzy2010@163.com.
  • Supported by:

    This study was supported by a grant from the Health Department of Hebei Province of China, No. 20120056, 20140314; the Funding Project for Introduced Abroad Study Personnel of Hebei Province of China, No. C2011003039.

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摘要：

既往研究显示，富集环境可保护多巴胺能神经元免受1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的损伤，但具体机制尚不十分清楚。生长相关蛋白43是一种在神经发育过程中与神经突生长和轴突再生密切相关的蛋白。我们推测富集环境可通过影响生长相关蛋白43的表达从而减轻多巴胺能神经元的损伤，实验设计你验证这一假说。将3月龄SAMP8小鼠分别在富集环境下饲养3个月，然后腹部皮下注射14 mg/kg 1-甲基-4-苯基-1,2,3,6-四氢吡啶4次，每次间隔2h。以水迷宫测试显示富集环境饲养的SAMP8小鼠比标准环境饲养的SAMP8小鼠在1-甲基-4-苯基-1,2,3,6-四氢吡啶干预后学习和记忆能力更强，以反转录PCR、免疫组化染色及Western blot分析显示，1-甲基-4-苯基-1,2,3,6-四氢吡啶干预后，富集环境饲养的SAMP8小鼠比标准环境饲养的SAMP8小鼠黑质中GAP43 mRNA和蛋白表达水平更高。上述数据显示，富集环境确实能提高1-甲基-4-苯基-1,2,3,6-四氢吡啶损伤SAMP8小鼠大脑黑质中生长相关蛋白43的表达，其可能是富集环境对抗1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导神经元损害的机制之一。

orcid:0000-0002-3255-8047(Zhen-Yun Yuan)

关键词: 帕金森病, 神经可塑性, SAMP8小鼠, 生长相关蛋白43, 大脑黑质, 学习记忆, 神经再生

Abstract:

An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43 (GAP-43) is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8 (SAMP8) mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that mRNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.

Key words: nerve regeneration, Parkinson’s disease, neural plasticity, senescence-accelerated mouse prone 8, growth associated protein-43, substantia nigra, learning and memory, neural regeneration