解剖学报 ›› 2023, Vol. 54 ›› Issue (2): 127-133.doi: 10.16098/j.issn.0529-1356.2023.02.001

• 神经生物学 •    下一篇

APP/PS1小鼠嗅球神经元的早期树突分支和长度及钾-氯离子共运转体2蛋白表达异常

陈搏雨1 江锦祥2 张家玮2 杨莉1*   

  1. 1. 广州大学生命科学学院基因与健康中心,广州 510006; 2. 华南师范大学生命科学学院,广州 510631
  • 收稿日期:2021-08-08 修回日期:2021-10-07 出版日期:2023-04-06 发布日期:2023-04-06
  • 通讯作者: 杨莉 E-mail:yang_li@gzhu.edu.cn
  • 基金资助:
    痴呆前期MBI及其与PFC-Str环路异常的相关性及分子标记物研究;阿尔茨海默症的诊治方法研究

Alterations in dendritic length and branch and K+ -Cl - cotransporter 2 expression of the olfactory bulb in young APP/PS1 mice

CHEN  Bo-yu1  JIANG  Jin-xiang2  ZHANG  Jia-wei2  YANG  Li1*   

  1. 1. Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou 510006, China;2. School of Life Sciences, South China Normal University, Guangzhou 510631, China
  • Received:2021-08-08 Revised:2021-10-07 Online:2023-04-06 Published:2023-04-06
  • Contact: YANG Li E-mail:yang_li@gzhu.edu.cn

摘要:

目的 探讨嗅球(OB)神经元的形态和相关蛋白的变化,探讨导致阿尔茨海默病(AD)嗅觉功能障碍的原因。   方法  采用高尔基-考克斯(Golgi-Cox)染色技术评估AD模型小鼠(APP/PS1小鼠)的OB和前梨状皮质(aPC)的神经元形态变化;使用Sholl分析对神经元的形态学进行测量;采用Western blotting检测蛋白质表达水平。   结果  高尔基-考克斯染色结果显示,在3~5月龄,该模型鼠尚未表现出AD的病理特征及认知障碍时,OB已经发生神经元树突长度和分支数量的显著减少。Western blotting检测发现,对神经元形态和突触功能至关重要的钾氯离子共转运体2(KCC2)蛋白表达在3~5 月龄APP/PS1小鼠的OB中显著降低。   结论  异常的神经元形态和KCC2信号途径改变可能是AD早期嗅觉功能障碍的基础;维持KCC2信号正常有望成为干预AD早期嗅觉异常的有效途径之一。 

关键词: 阿尔茨海默病, 嗅球, 梨状皮质, 钾-氯离子共转运体2, 免疫印迹法, 小鼠 

Abstract:

Objective  To study the morphology of olfactory bulb(OB) neurons and the change of related proteins, and explore the causes of olfactory dysfuction in Alzheimer’s disease(AD).    Methods  Golgi-Cox staining technique was used to evaluate the morphological changes of neurons in the OB and anterior piriform cortex (aPC) of APP/PS1 AD model mice. The morphology of neurons was determined by Sholl analysis. Western blotting was used to evaluate the levels of protein expression.    Results  The results of Golgi-Cox showed that the dendrite length and branch number reduced significantly in the OB neurons of 3-5-month-old APP/PS1 mice, an age that the mice did not show the pathological characteristics and cognitive impairment of AD. Western blotting analysis showed that levels of potassium chloride cotransporter 2(KCC2), a potassium chloride transporter crucial for neuronal morphology and synaptic function,   decreased significantly in the OB of 3-5-month-old APP/PS1 mice.    Conclusion  Abnormal neuronal morphology and KCC2 signal might be the basis of early olfactory dysfunction in AD. Thus, maintaining normal KCC2 signal may be one of the keys to intervene the olfactory abnormalities in the early stage of AD.  

Key words: Alzheimer’s disease, Olfactory bulb, Anterior piriform cortex, Potassium chloride cotransporter 2, Western blotting, Mouse

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