Enteric glial cell activation protects enteric neurons from damage due to diabetes in part via the promotion of neurotrophic factor release
Enteric glial cell activation protects enteric neurons from damage due to diabetes in part via the promotion of neurotrophic factor release
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DOI：
10.1111/nmo.13368
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发表时间：
2018-10-01
影响因子：
3.5
通讯作者：
Chang, M. -J.
中科院分区：
文献类型：
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作者：
Luo, P.;Liu, D.;Chang, M. -J.
研究背景糖尿病可导致肠神经系统发生病理改变。我们的目的是检测糖尿病大鼠肠神经元的动态变化，明确肠胶质细胞（EGC）在调节糖尿病大鼠肠神经元表达中的作用。方法采用单次注射链脲佐菌素（STZ）建立糖尿病大鼠。将动物随机分为糖尿病1周、4周、8周和16周组以及年龄匹配的对照组。通过免疫组织化学对 PGP9.5 和胶质纤维酸性蛋白 (GFAP) 免疫阳性细胞进行定量。通过蛋白质印迹法测定 PGP9.5、ChAT、nNOS、S-100 和 c-fos 的蛋白水平。通过 ELISA 检测神经生长因子 (NGF)、神经营养蛋白 3 (NT-3) 和胶质细胞源性神经营养因子 (GDNF) 的水平。 主要结果 给予 STZ 后观察到血糖升高和体重下降。 PGP9.5 表达在糖尿病回肠中没有变化。然而，糖尿病大鼠的回肠ChAT在16周后增加，nNOS在8周和16周后减少。疾病急性期肠神经元没有变性可能是 GFAP、S-100 和 c-fos 上调的结果。此外，糖尿病1周和/或4周后，回肠中NGF、NT-3、GDNF含量均有不同程度升高。利用EGCs和SH-SY5Y细胞在高血糖条件下的2个共培养模型，进一步证实了EGCs的支持作用。结论与推论肠道胶质细胞活化可以保护肠道神经元免受糖尿病急性期造成的损伤，部分机制是通过促进神经营养蛋白的释放。
BackgroundDiabetes can result in pathological changes to enteric nervous system. Our aim was to test the dynamic changes of enteric neurons and identify the role of enteric glial cells (EGCs) in regulating enteric neuron expression in diabetic rats.MethodsA single injection of streptozotocin (STZ) was used to establish diabetic rats. Animals were randomly distributed into diabetic 1-, 4-, 8-, and 16-week groups, as well as age-matched control groups. The PGP9.5- and glial fibrillary acidic protein (GFAP)-immunopositive cells were quantified by immunohistochemistry. The protein levels of PGP9.5, ChAT, nNOS, S-100, and c-fos were determined by western blotting. The levels of nerve growth factor (NGF), neurotrophin 3 (NT-3), and glial cell-derived neurotrophic factor (GDNF) were tested by ELISA.Key ResultsAn increase in blood glucose and a decrease in body weight were observed following STZ administration. PGP9.5 expression did not change in the diabetic ileum. However, ChAT increased after 16weeks, and nNOS decreased after 8 and 16weeks in theilea of diabetic rats. The absence of degeneration of enteric neurons during the acute stage of the disease could be the consequence of the up-regulation of GFAP, S-100, and c-fos. Moreover, the content of NGF, NT-3, and GDNF in theileum increased by varyingdegrees after 1 and/or 4weeks of diabetes. Using 2 co-culture models of EGCs and SH-SY5Y cells ina highglucosecondition, the supportive role of EGCs was further confirmed.Conclusions & InferencesEnteric glial cell activation can protect enteric neurons from damage due to diabetes in the acute stage of the disease, in part via the promotion of neurotrophin release.