Neuroprotective effects of olanzapine against rotenone-induced toxicity in PC12 cells

Authors: Ya-jie Xiong1, Yun-zhen Song1, Ying Zhu2, Wen-qing Zuo1, Yi-fan Zhao1, Xiao Shen1, Wen-juan Wang1, Ya-li Liu1, Jun-chao Wu1, Zhong-qin Liang1
1 Department of Pharmacology, Soochow University, Suzhou 215000, China
2 Department of Pharmacy, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou 215028, China
Correspondence to: Jun-chao Wu:, Zhong-qin Liang:,
DOI: 10.1038/s41401-020-0378-6
Received: 14 November 2019
Accepted: 13 February 2020
Advance online: 2 March 2020


Olanzapine is an antipsychotic drug used to treat patients with schizophrenia due to its lower incidence of extrapyramidal symptoms. Previous studies have shown that olanzapine activates AMP-activated protein kinase (AMPK), and induce autophagy in SH-SY5Y cell line. In this study, we investigated whether olanzapine protected against rotenone-induced neurotoxicity in PC12 cells. We showed that treatment with olanzapine increased the phosphorylation of AMPK in both dose- and time-dependent manners in PC12 cells. In addition, olanzapine activated autophagy and increased autophagic vacuoles. Furthermore, olanzapine pretreatment could protect PC12 cells from rotenone-induced apoptosis. Besides, olanzapine pretreatment could suppress the rotenone-induced depolarization of mitochondrial potential and thus protect the cells. Moreover, pretreatment with specific AMPK inhibitor compound C or with autophagy inhibitor 3-methyladenine impaired the protective effect of olanzapine on rotenone-treated PC12 cells. In summary, our results show for the first time that olanzapine ameliorates rotenone-induced injury by activating autophagy through AMPK pathway.
Keywords: olanzapine; AMPK; autophagy; neuroprotection; rotenone; PC12 cells

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