六羟多巴胺对成年小鼠黑质-纹状体系统多巴胺能神经元及其行为学的影响

谢明琦 陈治池 戚双双 王彤彤 张鹏 黄厚菊 周鹏 崔怀瑞 孙臣友

解剖学报 ›› 2017, Vol. 48 ›› Issue (4) : 361-374.

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解剖学报 ›› 2017, Vol. 48 ›› Issue (4) : 361-374. DOI: 10.16098/j.issn.0529-1356.2017.04.001
神经生物学

六羟多巴胺对成年小鼠黑质-纹状体系统多巴胺能神经元及其行为学的影响

  • 谢明琦1,2 陈治池1,2 戚双双3 王彤彤1,2  张鹏4  黄厚菊2,5  周鹏1,2  崔怀瑞1  孙臣友1,2*
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Effects of 6-hydroxydopamine on dopaminergic neurons in nigrostriatal system and on behavior of adult mice

  • XIE Ming-qi1,2 CHEN Zhi-chi1,2 QI Shuang-shuang3 WANG Tong-tong 1,2 ZHANG Peng4  HUANG Hou-ju 2,5 ZHOU Peng 1,2 CUI Huai-rui1  SUN Chen-you1, 2*
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摘要

目的 评估中脑黑质损伤后内源性神经前体细胞(NPCs)的增殖情况及其对黑质-纹状体系统损伤后恢复的促进作用。方法 向成年小鼠的一侧黑质(SN)注射六羟多巴胺(6-OHDA),损伤后3~35 d运用免疫荧光染色等方法,研究小鼠来自侧脑室、第三脑室、中脑水管周围及中脑部分NPCs的增殖,探索黑质中新生细胞的增殖及其向成熟神经元、多巴胺能神经元分化的情况,最后通过旷场和转棒实验检测小鼠行为学的变化(每组n=4~6)。 结果 黑质内注射6-OHDA引起的多巴胺能神经元损失可以明显增加第三脑室和中脑水管周围来自室管膜下区的NPCs的数目,以6-OHDA注射后的第7天最为明显,且6-OHDA注射后第21天黑质内新生细胞和新生多巴胺能神经元的数目增加达到高峰,这些变化可能导致了受损的黑质纹状体系统及小鼠行为学表现有部分恢复。 结论 促进内源性NPCs的增殖和分化将成为治疗帕金森病的理想手段。

Abstract

Objective To evaluate the proliferation of endogenous neural progenitor cells (NPCs) and its effect on the recovery of injured nigrostiatal system following mesencephalic substantia nigra lesion. Methods The proliferation of NPCs derived from the surrounding regions of the lateral ventricle, the third ventricle (3V) and the cerebral aqueduct (Aq) as well as the midbrain were investigated using immunofluorescent staining on days 3-35 following 6-hydroxydopamine (6-OHDA) injection into the unilateral substantia nigra (SN) of the adult mice. In addition, the proliferation of the SN newborn cells and their differentiation into mature neurons or dopaminergic neurons were explored. Finally, behavioral changes of mice were examined by open field and rotarod tests(n=4-6,each group).
Results The 6-OHDA-induced loss of dopaminergic neurons in the SN significantly increased the numbers of NPCs from the subventricular zone in the surrounding regions of 3V and Aq, which was most obvious on day 7 following 6-OHDA injection. The number of SN new-born cells and new-generated dopaminergic neurons reached to the peak on day 21 following 6-OHDA injection, which possibly resulted in a partial restoration in the lesioned nigrastriatum system and behavioral performance of mice. Conclusion It might be an ideal strategy to deal with Parkinson’s disease by promoting the proliferation and differentiation of endogenous NPCs.

关键词

帕金森病 / 黑质 / 神经前体细胞 / 多巴胺能神经元 / 六羟多巴胺 / 免疫荧光 / 小鼠

Key words

Parkinson’s disease
/ Substantia nigra / Neural progenitor cell / Dopaminergic neurons / 6-Hydroxydopamine / Immunofluorescence / Mouse

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谢明琦 陈治池 戚双双 王彤彤 张鹏 黄厚菊 周鹏 崔怀瑞 孙臣友. 六羟多巴胺对成年小鼠黑质-纹状体系统多巴胺能神经元及其行为学的影响[J]. 解剖学报. 2017, 48(4): 361-374 https://doi.org/10.16098/j.issn.0529-1356.2017.04.001
XIE Ming-qi CHEN Zhi-chi QI Shuang-shuang WANG Tong-tong ZHANG Peng HUANG Hou-ju ZHOU Peng CUI Huai-rui SUN Chen-you. Effects of 6-hydroxydopamine on dopaminergic neurons in nigrostriatal system and on behavior of adult mice[J]. Acta Anatomica Sinica. 2017, 48(4): 361-374 https://doi.org/10.16098/j.issn.0529-1356.2017.04.001

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基金

别孕烯醇酮促进PD小鼠多巴胺能神经元新生的作用及机制;Al|opregnanolone诱导AD小鼠黑质多巴胺能神经元增多的机制研究;CD133追综APα诱导的6-OHDA PD小鼠新生多巴胺能神经元起源的应用研究;CD133+室管膜细胞的建立及追踪新生多巴胶能神经元起源的应用研究

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