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Melatonin attenuates methamphetamine‐induced inhibition of proliferation of adult rat hippocampal progenitor cells in vitro
Author(s) -
Ekthuwapranee Kasima,
Sotthibundhu Areechun,
Govitrapong Piyarat
Publication year - 2015
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12225
Subject(s) - meth , progenitor cell , melatonin , cell growth , methamphetamine , hippocampal formation , neural stem cell , biology , endocrinology , microbiology and biotechnology , medicine , chemistry , pharmacology , stem cell , biochemistry , monomer , organic chemistry , acrylate , polymer
Methamphetamine ( METH ) is an extremely addictive stimulatory drug. A recent study suggested that METH may cause an impairment in the proliferation of hippocampal neural progenitor cells, but the underlying mechanism of this effect remains unknown. Blood and cerebrospinal levels of melatonin derive primarily from the pineal gland, and that performs many biological functions. Our previous study demonstrated that melatonin promotes the proliferation of progenitor cells originating from the hippocampus. In this study, hippocampal progenitor cells from adult Wistar rats were used to determine the effects of METH on cell proliferation and the mechanisms underlying these effects. We investigated the effects of melatonin on the METH ‐induced alteration in cell proliferation. The results demonstrated that 500 μ m METH induced a decrease (63.0%) in neurosphere cell proliferation and altered the expression of neuronal phenotype markers in the neurosphere cell population. Moreover, METH induced an increase in the protein expression of the tumor suppressor p53 (124.4%) and the cell cycle inhibitor p21 CIP 1 (p21) (128.1%), resulting in the accumulation of p21 in the nucleus. We also found that METH altered the expression of the N ‐methyl‐ d ‐aspartate ( NMDA ) receptor subunits NR 2A (79.6%) and NR 2B (126.7%) and Ca 2+ /calmodulin‐dependent protein kinase II ( CAMKII ) (74.0%). In addition, pretreatment with 1 μ m melatonin attenuated the effects induced by METH treatment. According to these results, we concluded that METH induces a reduction in cell proliferation by upregulating the cell cycle regulators p53/p21 and promoting the accumulation of p21 in the nucleus and that melatonin ameliorates these negative effects of METH .