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Differential expression of glial cell line-derived neurotrophic factor splice variants in the mouse brain

Neural Regeneration Research 2020年第2期15卷 270-276页

作者： Xiao-He Gu Heng Li Lin Zhang Tao He Xiang Chai He Wei Dian-Shuai Gao Department of Anatomy and Neurobiology Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurosurgery First Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina

Glial cell line-derived neurotrophic factor(gdnf) plays a critical role in neuronal survival and function. gdnf has two major splice variants in the brain,α-pro-gdnf and β-pro-gdnf, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the gdnf splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-gdnf in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-gdnf expression was significantly greater than that of α-pro-gdnf in the mouse brain. In contrast, at the protein level,α-pro-gdnf expression was markedly greater than that of β-pro-gdnf. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the gdnf splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-gdnf expression, but not with α-pro-gdnf expression. This suggests that the differential expression of α-and β-pro-gdnf in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the gdnf isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016.

关键词： Δ78 locus brain region dopaminergic neurons glial cell line-derived neurotrophic factor mouse brain precursor protein α-pro-gdnf β-pro-gdnf sorting protein-related receptor with A-type repeats splice variants

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