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

ABSTRACT: 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, ?-pro-GDNF and ?-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 ?- and ?-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, ?-pro-GDNF expression was significantly greater than that of ?-pro-GDNF in the mouse brain. In contrast, at the protein level, ?-pro-GDNF expression was markedly greater than that of ?-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 ?-pro-GDNF expression, but not with ?-pro-GDNF expression. This suggests that the differential expression of ?- and ?-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.

SUBMITTER: Gu XH

PROVIDER: S-EPMC6905338 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Gu Xiao-He XH Li Heng H Zhang Lin L He Tao T Chai Xiang X Wei He H Gao Dian-Shuai DS

Neural regeneration research 20200201 2

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 quantita ...[more]

PMID: 31552899

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Project description:The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes. Its special anatomical and physiological structure renders it susceptible to nerve injury. The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone. This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions. Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. In monoculture, glial cell line-derived neurotrophic factor promoted the migration of Schwann cells, but it did not have effects on the migration of astrocytes. In the co-culture system, glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells. Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes. However, in the co-culture system, brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree. These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone. This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.

Dataset Information

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

Publications

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

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