AUTHOR=Hua Ye , Yang Beibei , Chen Qiang , Zhang Ji , Hu Jun , Fan Yi 

TITLE=Activation of α7 Nicotinic Acetylcholine Receptor Protects Against 1-Methyl-4-Phenylpyridinium-Induced Astroglial Apoptosis

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 13 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00507

DOI=10.3389/fncel.2019.00507

ISSN=1662-5102

ABSTRACT=Astrocytes, as the largest population of glial subtype, play crucial roles in normal brain function and pathological conditions, such as Parkinson’s disease (PD). Restoring the functions of astrocyte is a promising new therapeutic target for PD. Astrocytes can express multiple types of neurotransmitter receptors, including functional α7 nicotinic acetylcholine receptor (α7nAChR). Previously, we found that a non-selective α7nAChR agonist nicotine exerted a protective effect against H2O2-induced astrocyte apoptosis via an α7nAChR-dependent. However, the molecular mechanism of the anti-apoptotic response of astroglial α7nAChR has not been studied. In the present study, using pharmacological inhibition and genetic knockout of α7nAChR, we assessed the anti-apoptotic effects of an α7nAChR agonist PNU-282987 in primary cultured astrocytes treated with 1-methyl-4-phenylpyridinium (MPP+). PNU-282987 promoted the viability of astrocytes, alleviated MPP+-induced apoptosis, and decreased the number of GFAP+/TUNEL+ cells. Meanwhile, PNU-282987 up-regulated the expression of the anti-apoptotic protein Bcl-2 and down-regulated the expression of the apoptotic protein Bax and cleaved-caspase-3. Moreover, the suppression of the JNK-p53-caspase-3 signaling may underlie the neuroprotective property of PNU-282987. Therefore, PNU-282987 ameliorate astroglial apoptosis induced by MPP+ through α7nAChR-JNK-p53 signaling. Our findings suggest that PNU-282987 may be a potential drug for restoring astroglial functions in the treatment of PD.