食蟹猴纹状体内注射α-突触核蛋白预制原纤维对嗅球病理改变的影响

doi:10.11958/20221892

天津医药 ›› 2023, Vol. 51 ›› Issue (6): 586-589.doi: 10.11958/20221892

食蟹猴纹状体内注射α-突触核蛋白预制原纤维对嗅球病理改变的影响

丁雨潇¹(), 粟璟曦¹, 宋琼¹, 王丽惠¹, 吴日宝¹, 况昕宇¹, 苏迎¹, 邹春林¹^,²^,^△

1 广西医科大学基础医学院转化医学研究中心"长寿与老年相关疾病"教育部重点实验室，神经科学研究所“广西脑科学研究”重点实验室（邮编530021）
2 再生医学与医用生物资源开发应用省部共建协同创新中心，广西再生医学重点实验室

收稿日期:2022-12-02 修回日期:2023-03-09 出版日期:2023-06-15 发布日期:2023-06-20
通讯作者: ^△E-mail：zouchunlin@sohu.com
作者简介:丁雨潇（1999），女，硕士在读，主要从事帕金森病治疗方面研究。E-mail：dingyuxiao2016@163.com
基金资助:
国家自然科学基金资助项目(81971191)

Effect of intra-striatal injection of α-Synuclein PFF on pathological changes of olfactory bulb in macaca fascicularis

DING Yuxiao¹(), SU Jingxi¹, SONG Qiong¹, WANG Lihui¹, WU Ribao¹, KUANG Xinyu¹, SU Ying¹, ZOU Chunlin¹^,²^,^△

1 Center for Translational Medicine, Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Institute of Neuroscience and Guangxi Key Laboratory of Brain Science， School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China
2 Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine

Received:2022-12-02 Revised:2023-03-09 Published:2023-06-15 Online:2023-06-20
Contact: ^△E-mail：zouchunlin@sohu.com

丁雨潇, 粟璟曦, 宋琼, 王丽惠, 吴日宝, 况昕宇, 苏迎, 邹春林. 食蟹猴纹状体内注射α-突触核蛋白预制原纤维对嗅球病理改变的影响[J]. 天津医药, 2023, 51(6): 586-589.

DING Yuxiao, SU Jingxi, SONG Qiong, WANG Lihui, WU Ribao, KUANG Xinyu, SU Ying, ZOU Chunlin. Effect of intra-striatal injection of α-Synuclein PFF on pathological changes of olfactory bulb in macaca fascicularis[J]. Tianjin Medical Journal, 2023, 51(6): 586-589.

摘要/Abstract

摘要：

目的探讨α-突触核蛋白预制原纤维（α-Syn PFF）纹状体注射后能否生成病理性α-突触核蛋白（α-Syn），并从纹状体传播至嗅球，从而引起嗅球中神经元损伤。方法 3只健康雌性食蟹猴双侧纹状体注射α-Syn PFF作为实验组，以脑立体定向注射手术，将300 μg α-Syn PFF（7 g/L）注射到双侧纹状体的6个位点，即每侧纹状体壳核头部注射60 μg，体部注射60 μg，尾部注射30 μg。另2只健康雌性食蟹猴相同部位注射同等剂量磷酸盐缓冲液（PBS）作为对照组。注射2年后，实验猴行安乐死，取出嗅球经固定和切片，然后经尼氏染色检测组织病理改变，免疫组织化学染色检测磷酸化α-Syn（pS129）、酪氨酸羟化酶（TH）、双皮质素（DCX）的表达情况。结果实验组与对照组比较，嗅球中存在pS129阳性聚集体；实验组TH和DCX阳性神经元数量较对照组均显著减少[TH：（27.00±11.22）个vs.（65.80±36.54）个；DCX：（67.60±17.23）个vs.（88.30±19.89）个]。结论食蟹猴纹状体注射α-Syn PFF产生的病理性α-Syn可从纹状体传播至嗅球造成嗅球神经元损伤，诱导嗅球中多巴胺能神经元丢失，并抑制新生神经元生成。

关键词: 帕金森病, α突触核蛋白, 嗅球, 成束猴, 免疫组织化学

Abstract:

Objective To investigate whether pathological α-Synuclein (α-Syn) can be generated after striatal injection of α-Syn preformed fibrils (PFF), and then spread from striatum to olfactory bulb, thereby causing neuronal damage in olfactory bulb. Methods Three healthy female macaca fascicularis injected with α-Syn PFF into the bilateral striatum were used as the experimental group. 300 μg α-Syn PFF (7 g/L) was injected into each side of the striatal putaminal nucleus with 60 μg in head, 60 μg in body and 30 μg in tail. The other two healthy female macaca fascicularis were injected with PBS as the control group. Two years after the injection, macaca fascicularis were killed. Pathological changes were detected by Nissl staining, and immunohistochemistry was performed to examine the expression levels of phosphorylated α-Synuclein (pS129), tyrosine hydroxylase (TH) and doublecortin (DCX) in olfactory bulb. Results Compared to the control group, pS129 positive aggregates were found in olfactory bulb of the experimental group. Besides, the number of TH-positive and DCX-positive neurons were significantly decreased in the experimental group [TH:(27.00±11.22) vs. (65.80±36.54); DCX: (67.60±17.23) vs. (88.30±19.89)]. Conclusion Pathological α-Syn can spread from striatum to olfactory bulb and induce the loss of dopaminergic neurons, inhibiting the generation of newborn neurons in olfactory bulb of macaca fascicularis.

Key words: Parkinson disease, alpha-synuclein, olfactory bulb, macaca fascicularis, immunohistochemistry

中图分类号:

R742.5

图/表 4

图1 嗅球组织尼氏染色

Fig.1 Nissl staining in olfactory bulb

图2 免疫组织化学染色嗅球组织pS129表达

Fig.2 Immunohistochemistry staining of pS129 in olfactory bulb

图3 免疫组织化学染色检测嗅球TH阳性神经元数量

Fig.3 The number of TH-positive neurons detected by immunohistochemistry staining in olfactory bulb

图4 免疫组织化学染色检测嗅球DCX阳性新生神经元数量

Fig.4 The number of DCX-positive new neurons detected by immunohistochemistry staining in olfactory bulb

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食蟹猴纹状体内注射α-突触核蛋白预制原纤维对嗅球病理改变的影响

Effect of intra-striatal injection of α-Synuclein PFF on pathological changes of olfactory bulb in macaca fascicularis

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