中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (7): 1111-1118.doi: 10.4103/1673-5374.211190

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

侧脑室下区成年神经干细胞功能失调会导致糖尿病嗅觉缺陷

  

  • 收稿日期:2017-04-05 出版日期:2017-07-15 发布日期:2017-07-15
  • 基金资助:

    国家自然科学基金(81370448, 81570725)

Adult neural stem cell dysfunction in the subventricular zone of the lateral ventricle leads to diabetic olfactory defects

Yu-hong Jing1, 2, Chu-chu Qi1, Li Yuan1, Xiang-wen Liu1, Li-ping Gao3, Jie Yin1   

  1. 1 Institute of Anatomy and Histology & Embryology and Neuroscience, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, China; 2 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, Gansu Province, China; 3 Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu Province, Chin
  • Received:2017-04-05 Online:2017-07-15 Published:2017-07-15
  • Contact: Jie Yin, M.D., yinjie@lzu.edu.cn.
  • Supported by:

    This work is partly supported by the National Natural Science Foundation of China, No. 81370448, 81570725.

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摘要：

灵敏的气味识别有赖于嗅球结构的可塑性，该可塑性依赖于侧脑室下区新生神经元向嗅球的迁移和整合。实验以此分析了糖尿病大鼠侧脑室下区神经干细胞状态和嗅觉功能的关系。将SD大鼠股静脉单次注射链脲佐菌素诱导构建1型糖尿病大鼠模型发现，链脲佐菌素注射后2个月，糖尿病模型大鼠嗅觉敏感性下降，其侧脑室下区BrdU阳性细胞及BrdU+/DCX+双标记的细胞数量显著低于同年龄对照大鼠。免疫印迹结果显示糖尿病模型大鼠侧脑室下区胰岛素受体水平、糖原合成激酶3β的磷酸化水平、β-连环蛋白表达均下调。上述现象说明，糖尿病可导致胰岛素缺陷，对糖原合成激酶3β产生负性调节作用，使β-连环蛋白降解增加。这些变化抑制了侧脑室下区神经干细胞的增殖和分化及嗅球结构可塑性下降，从而损害了嗅觉探测的灵敏度。

ORCID:0000-0002-3131-5254(Jie Yin)

 

关键词: 神经再生, 糖尿病脑病, 成体神经干细胞, 嗅觉功能, 侧脑室下区, 增殖, 分化, 大鼠, 胰岛素, 糖原合成激酶3β, β-连环蛋白, 1型糖尿病

Abstract:

Sensitive smell discrimination is based on structural plasticity of the olfactory bulb, which depends on migration and integration of newborn neurons from the subventricular zone. In this study, we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus. Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats. Two months after injection, olfactory sensitivity was decreased in diabetic rats. Meanwhile, the number of BrdU-positive and BrdU+/DCX+ double-labeled cells was lower in the subventricular zone of diabetic rats compared with age-matched normal rats. Western blot results revealed downregulated expression of insulin receptor β, phosphorylated glycogen synthase kinase 3β, and β-catenin in the subventricular zone of diabetic rats. Altogether, these results indicate that diabetes mellitus causes insulin deficiency, which negatively regulates glycogen synthase kinase 3β and enhances β-catenin degradation, with these changes inhibiting neural stem cell proliferation. Further, these signaling pathways affect proliferation and differentiation of neural stem cells in the subventricular zone. Dysfunction of subventricular zone neural stem cells causes a decline in olfactory bulb structural plasticity and impairs olfactory sensitivity in diabetic rats.

Key words: nerve regeneration, diabetic encephalopathy, adult neural stem cells, olfactory function, subventricular zone, proliferation, glycogen synthase kinase 3 beta, β-catenin, differentiation, rats, insulin, type 1 diabetes mellitus, neural regeneration