Activation of α7 nicotinic acetylcholine receptors protects astrocytes against oxidative stress-induced apoptosis: Implications for Parkinson's disease
Activation of α7 nicotinic acetylcholine receptors protects astrocytes against oxidative stress-induced apoptosis: Implications for Parkinson's disease
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α7 烟碱乙酰胆碱受体的激活可保护星形胶质细胞免受氧化应激诱导的细胞凋亡：对帕金森病的影响
DOI：
10.1016/j.neuropharm.2014.11.028
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发表时间：
2015-04-01
影响因子：
4.7
通讯作者：
Hu, Jun
中科院分区：
文献类型：
--
作者：
Liu, Yuan;Zeng, Xiaoning;Hu, Jun
星形胶质细胞与帕金森病（PD）相关的免疫反应有关。抑制星形胶质细胞凋亡是治疗PD的新策略。最近的研究表明，α 7烟碱乙酰胆碱受体（α 7-nAChR）表达的胶质细胞之间的炎症和神经退行性疾病的PD的关键环节。然而，很少有人知道他们的贡献星形胶质细胞凋亡的发展过程中，这种疾病。在本研究中，我们发现，尼古丁对H2 O2诱导的星形胶质细胞凋亡和胶质细胞源性神经营养发挥保护作用。因子（GDNF）下调，这种作用被α 7-nAChR选择性拮抗剂消除。潜在的机制可能涉及减轻线粒体膜电位损失，稳定Bax/Bcl-2平衡，并通过α 7-nAChR激活抑制切割的caspase-9活性。全身给予尼古丁可显著缓解MPTP诱导的症状，保护多巴胺能神经元免于变性，抑制黑质背侧部（SNpc）中的星形胶质细胞和小胶质细胞活化，并通过激活α 7-nAChR阻断纹状体中GDNF的减少。综上所述，这些发现首次证明，尼古丁通过刺激α 7-nAChR通过线粒体途径抑制H2 O2诱导的星形胶质细胞凋亡。靶向星形胶质细胞中表达的α 7-nAChR可能是治疗神经退行性疾病的新治疗策略。(C)2015由Elsevier Ltd.出版
Astrocytes have been implicated in the immune responses associated with Parkinson's disease (PD). Inhibition of astrocyte apoptosis is a novel strategy for the treatment of PD. Recent studies suggest that alpha 7 nicotinic acetylcholine receptors (alpha 7-nAChRs) expressed in glial cells are critical links between inflammation and neurodegeneration in PD. However, little is known about their contribution to astrocyte apoptosis during the development of this disorder. In the present study, we showed that nicotine exerts a protective effect on H2O2-induced astrocyte apoptosis and glial cell-derived neurotrophic. factor (GDNF) downregulation, and this effect was abolished by an alpha 7-nAChR-selective antagonist. The underlying mechanisms might involve alleviation of mitochondrial membrane potential loss, stabilization of the Bax/Bcl-2 balance, and inhibition of cleaved caspase-9 activity through alpha 7-nAChR activation. Systemic administration of nicotine dramatically alleviated MPTP-induced symptoms, protected dopaminergic neurons against degeneration, inhibited astrocytes and microglia activation in the substantia nigra pars compacta (SNpc) and blocked the decrease of GDNF in the striatum by activating alpha 7-nAChRs. Taken together these findings demonstrate, for the first time, that nicotine suppresses H2O2-induced astrocyte apoptosis via the mitochondrial pathway through the stimulation of alpha 7-nAChRs. Targeting alpha 7-nAChRs expressed in astrocytes may be a novel therapeutic strategy for the treatment of neurodegenerative disorders. (C) 2015 Published by Elsevier Ltd.