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Intranasal Administration of GDNF Protects Against Neural Apoptosis in a Rat Model of Parkinson’s Disease Through PI3K/Akt/GSK3β Pathway

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Abstract

Glial cell line-derived neurotrophic factor (GDNF) plays important roles in protecting the damaged or dying dopamine neurons in the animal models of Parkinson’s disease (PD). This study was to determine the effect and mechanisms of GDNF on the apoptosis of neurons in 6-hydroxydopamine (6-OHDA) induced Parkinson’s disease model of rats. Healthy male Sprague–Dawley rats (220–240 g) were randomly divided into six groups (n = 10). 6-OHDA was used to establish the PD rat model. Tyrosine hydroxylase (TH) immunohistochemistry was used to assess the neuron loss in 6-OHDA-lesioned rats. TUNEL and western blot were used to identify the effects and mechanisms of GDNF in the rat model of PD. The numbers of TH-positive neurons in the 6-OHDA-injected lesioned substantia nigra (SN) decreased significantly compared with the Sham group. GDNF treatment effectively ameliorated the apoptosis of neuronal cells in SN induced by 6-OHDA. In addition, GDNF significantly increased serine protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK3β) phosphorylation induced by 6-OHDA. In contrast, application of LY294002 or triciribine reversed the roles of GDNF in PD models. The results implicated that the anti-apoptosis effects of GDNF in neurons might be mediated through PI3K/Akt/GSK3β pathway. Therefore, GDNF may be a promising agent for PD treatment.

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Acknowledgements

This work was supported by The First Affiliated Hospital of Zhengzhou University and National Natural Science Foundation of China (81501109, U1504813).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China

    Peijian Yue, Xuejing Wang, Xuebing Ding & Junfang Teng

  2. Department of Neurological Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Lin Gao

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Correspondence to Junfang Teng.

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Yue, P., Gao, L., Wang, X. et al. Intranasal Administration of GDNF Protects Against Neural Apoptosis in a Rat Model of Parkinson’s Disease Through PI3K/Akt/GSK3β Pathway. Neurochem Res 42, 1366–1374 (2017). https://doi.org/10.1007/s11064-017-2184-1

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  • DOI: https://doi.org/10.1007/s11064-017-2184-1

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