Intranasal Administration of GDNF Protects Against Neural Apoptosis in a Rat Model of Parkinson's Disease Through PI3K/Akt/GSK3beta Pathway
Intranasal Administration of GDNF Protects Against Neural Apoptosis in a Rat Model of Parkinson's Disease Through PI3K/Akt/GSK3beta Pathway
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鼻内给予 GDNF 通过 PI3K/Akt/GSK3beta 通路防止帕金森病大鼠模型中的神经细胞凋亡
DOI：
10.1007/s11064-017-2184-1
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Junfang Teng
中科院分区：
文献类型：
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作者：
Peijian Yue;Lin Gao;Xuejing Wang;Xuebing Ding;Junfang Teng
胶质细胞源性神经营养因子（GDNF）在帕金森病（PD）动物模型中对受损或死亡的多巴胺神经元具有重要的保护作用。本研究旨在探讨GDNF对6-羟基多巴胺（6-OHDA）诱导的帕金森病大鼠模型神经元凋亡的影响及其机制。健康雄性Sprague-Dawley大鼠（220-240 g）随机分为6组（n = 10）。6-采用OHDA建立PD大鼠模型。酪氨酸羟化酶（TH）免疫组织化学方法用于评估6-OHDA损伤大鼠的神经元损失。采用TUNEL法和westernblot法观察GDNF对PD大鼠模型的作用及机制。6-OHDA组黑质TH阳性神经元数较假手术组明显减少。GDNF处理能有效地减轻6-OHDA诱导的黑质神经细胞凋亡。此外，GDNF显著增加6-OHDA诱导的丝氨酸蛋白激酶B（Akt）和糖原合成酶激酶3 β（GSK 3 β）磷酸化。相比之下，LY 294002或triciribine的应用逆转了GDNF在PD模型中的作用。结果提示GDNF可能通过PI 3 K/Akt/GSK 3 β通路发挥抗神经元凋亡作用。因此，GDNF可能是一种有希望的PD治疗药物
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 (GSK3beta) 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/GSK3beta pathway. Therefore, GDNF may be a promising agent for PD treatment