Activation Of Î±7 Nicotinic Acetylcholine Receptors Protects Astrocytes Against Oxidative Stress-Induced Apoptosis: Implications For Parkinson'S Disease
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 Î±7 nicotinic acetylcholine receptors (Î±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 Î±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 Î±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 Î±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 Î±7-nAChRs. Targeting Î±7-nAChRs expressed in astrocytes may be a novel therapeutic strategy for the treatment of neurodegenerative disorders.
Digital Object Identifier (DOI)
Liu, Yuan; Zeng, Xiaoning; Hui, Yujian; Zhu, Chenlei; Wu, Jie; Taylor, Devin H.; Ji, Juan; Fan, Weimin; Huang, Zuhu; and Hu, Jun, "Activation Of Î±7 Nicotinic Acetylcholine Receptors Protects Astrocytes Against Oxidative Stress-Induced Apoptosis: Implications For Parkinson'S Disease" (2015). Neurobiology. 404.