中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (12): 1969-1975.doi: 10.4103/1673-5374.197140

• 原著:退行性病与再生 • 上一篇    下一篇

皮质性调节对帕金森病模型的神经保护:投射神经元和中间神经元的不同作用

  

  • 收稿日期:2016-11-29 出版日期:2016-12-31 发布日期:2016-12-31
  • 基金资助:
    中国国家自然科学基金项目(81471288)

Cortical regulation of striatal projection neurons and interneurons in a Parkinson’s disease rat model

Jia-jia Wu1, 2, Si Chen1, Li-si Ouyang1, Yu Jia1, Bing-bing Liu3, Shu-hua Mu4, Yu-xin Ma1, Wei-ping Wang1, Jia-you Wei1, You-lan Li1, Zhi Chen1, Wan-long Lei1, *   

  1. 1 Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China 2 Periodical Center, the Tird Afliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China 3 Department of Anesthesiology, Guangdong No. 2 Provincial People’s Hospital, Guangdong Provincial Emergency Hospital, Guangzhou, Guangdong Province, China 4 Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong Province, China
  • Received:2016-11-29 Online:2016-12-31 Published:2016-12-31
  • Contact: Wan-long Lei, Ph.D., leiwl@mail.sysu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81471288.

摘要:

纹状体神经元分为投射神经元和中间神经元。不同类型纹状体神经元对不同种类脑损伤的敏感度不同。实验在右前脑内侧束注射6-羟基多巴胺诱导大鼠多巴胺耗竭和/或在大脑皮质运动M1区同时注射鹅膏蕈氨酸致运动皮质损毁。免疫组化和Western blot结果显示,单纯多巴胺耗竭后,大鼠纹状体中分子量为32 kDa的多巴胺和cAMP调节的磷蛋白(DARPP32)、钙结合蛋白以及μ-阿片受体标记的投射神经元出现缺失,神经肽Y阳性中间神经元数量增加,而运动皮质损毁可逆转上述变化,但单纯多巴胺耗竭和皮质病变都对小清蛋白阳性中间神经元的数量没有影响。说明纹状体投射神经元和中间神经元对多巴胺耗竭的敏感性不同,大脑皮质运动M1区损毁抑制6-羟基多巴胺致纹状体功能障碍和损伤,这可能为临床治疗帕金森提供了新的思路和可能新方法。

orcid: 0000-0002-0555-7428 (Wan-long Lei)

关键词: 神经再生, 运动皮质损毁, 多巴胺能神经元, GABA能神经元, 分子量为32 kDa的多巴胺和cAMP调节的磷蛋白(DARPP32), 钙结合蛋白, μ-阿片受体, 神经肽Y, 小清蛋白, 帕金森病

Abstract: Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/ or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in signifcant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 kDa, calbindin, and μ-opioid receptor, while cortical lesions reversed these pathological changes. Afer dopaminergic deletion, the number of neuropeptide Y-positive striatal interneurons markedly increased, which was also inhibited by cortical lesioning. No noticeable change in the number of parvalbumin-positive interneurons was found in 6-hydroxydopamine-treated rats. Striatal projection neurons and interneurons show different susceptibility to dopaminergic depletion. Further, cortical lesions inhibit striatal dysfunction and damage induced by 6-hydroxydopamine, which provides a new possibility for clinical treatment of Parkinson’s disease.

Key words: nerve regeneration, motor cortex lesions, dopaminergic neurons, GABAergic neurons, Darpp32, calbindin, μ-opioid receptor, neuropeptide Y, parvalbumin, neural regeneration