Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway.
Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway.
Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Jintao
J
Wu
Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Dexiao
D
Zhu
Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Jing
J
Zhang
Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Guibao
G
Li
Department of Psychiatry, School of Medicine, Shandong University, Jinan, Shandong, 250012 China.
Zengxun
Z
Liu
Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012, China. Electronic address: sunjinhao@gmail.com.
Jinhao
J
Sun
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018021:Lithium Chloride / Q000008:administration & dosage*; D008694:Methamphetamine / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D009498:Neurotoxins / Q000633:toxicity; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D018696:Neuroprotective Agents; D009498:Neurotoxins; D008694:Methamphetamine; C546845:mTOR protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride
Akt; GSK3β; Lithium; Methamphetamine; Neurotoxicity; mTOR