Melatonin attenuates methamphetamine-induced neuroinflammation through the melatonin receptor in the SH-SY5Y cell line.
Methamphetamine is a well-known psychostimulant drug, the abuse of which is a serious worldwide public health issue. In addition to its addictive effect, methamphetamine exposure has been shown to be associated with neuroinflammation in several brain areas. Several lines of evidence indicate that TNFα plays an important role in the methamphetamine-induced neuroinflammatory processes that result in apoptotic cell death. Many investigators have demonstrated the anti-neuroinflammatory effects of melatonin, but the mechanism by which this occurs still needs to be explored. In this study, we investigated the effect of methamphetamine on TNFα expression and NFκB activation in the neuroblastoma cell line SH-SY5Y. We demonstrated the time-dependent effect of methamphetamine on the induction of TNFα expression as well as IκB degradation and NFκB nuclear translocation. Furthermore, we investigated the effect of melatonin on methamphetamine-induced TNFα overexpression and NFκB activation. The results showed that pretreatment with 100nM melatonin could prevent the TNFα overexpression caused by methamphetamine exposure. This attenuating effect was prevented by pre-incubation with luzindole, an antagonist of the melatonin MT1/MT2 receptors. Furthermore, methamphetamine-induced IκB degradation and NFκB nuclear translocation were also suppressed by pretreatment with melatonin, and pretreatment with luzindole diminished these protective effects. MT2 knockdown by siRNA abrogated the anti-inflammatory effect exerted by melatonin. From these findings, we propose that melatonin exerts its protective effects on methamphetamine-induced neuroinflammation through the membrane receptor, at least in part MT2 subtype, in the SH-SY5Y neuroblastoma cell line.
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom 73170, Thailand.
Pawaris
P
Wongprayoon
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom 73170, Thailand; Center for Neuroscience and Department of Pharmacology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. Electronic address: piyarat.gov@mahidol.ac.th.
Piyarat
P
Govitrapong
D000975:Antioxidants / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000697:Central Nervous System Stimulants / Q000633:toxicity; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008550:Melatonin / Q000627:therapeutic use*; D008694:Methamphetamine / Q000633:toxicity; D009447:Neuroblastoma / Q000473:pathology; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014363:Tryptamines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D000697:Central Nervous System Stimulants; D016895:Culture Media, Serum-Free; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D034741:RNA, Small Interfering; D044094:Receptors, Melatonin; D014363:Tryptamines; D014409:Tumor Necrosis Factor-alpha; C057154:luzindole; D008694:Methamphetamine; D008550:Melatonin
Melatonin; Melatonin receptor; Methamphetamine; NFκB; Neuroinflammation; TNFα