title: Lithium protects dopaminergic cells from rotenone toxicity via autophagy enhancement.
abstract: BACKGROUND
  Previous studies have indicated that enhancement of autophagy lysosome pathway may be beneficial for Parkinson's disease (PD), in which aberrant accumulation of aggregated/misfolded proteins and mitochondrial dysfunction are considered as crucial pathogenesis. Recently, a number of studies have suggested the neuroprotective effects of lithium in models of several neurodegenerative diseases including PD. However, the exact mechanisms underlying this neuroprotection remain unclear. In our study, rotenone-exposed SH-SY5Y cells were used as an in vitro parkinsonian model to assess the autophagy-enhancing effect of lithium and the underlying mechanisms were further investigated.
  
  
  RESULTS
  Similar to the common used autophagy enhancer rapamycin (Rap, 0.2 μM), lithium (LiCl, 10 mM) significantly recovered the shrinkage of SH-SY5Y cells, and alleviated rotenone-induced cell apoptosis, mitochondrial membrane potential reduction and reactive oxygen species accumulation. Furthermore, the protective effects induced by LiCl were partially blocked by the co-treatment of autophagy inhibitors such as 3-methyladenine (3-MA, 10 mM) or chloroquine (CHL, 10 μM). Moreover, 3-MA or Chl suppressed LiCl-induced autophagy in the immunoblot assay. In addition, the co-localization of LC3 and mitochondria and the preservation of mitochondrial function within LiCl-treated cells were observed, confirming that the damaged mitochondria were cleared through autophagy (mitophagy).
  
  
  CONCLUSIONS
  These findings suggested that lithium exerted neuroprotection against rotenone-induced injuries partially through the autophagy pathway. Pharmacologically induction of autophagy by lithium may represent a novel therapeutic strategy as a disease-modifier in PD.
authors.affiliation: Department of Emergency, Central Hospital of Wuhan, Wuhan, Hubei, China. 2013houl@163.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. nianxiong@hust.edu.cn.
authors.forename: Nian
authors.initials: N
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. lingliuhust@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. kingshayellow@163.com.
authors.forename: Jinsha
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. bbhc1989@sina.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. zgx8902@126.com.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. lijiehsb@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. xuxiaoyun1024@163.com.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Alcohol and Drug Abuse, Department of Psychiatry and Harvard NeuroDiscovery Center, Harvard Medical School and Laboratory of Psychiatric Neurogenomics, McLean Hospital, Belmont, MA, USA. zhicheng_lin@hms.harvard.edu.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Neurology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China. wangtaowh@hust.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D000978:Antiparkinson Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012402:Rotenone; D020782:Matrix Metalloproteinases; D018021:Lithium Chloride