共 51 条
Melatonin attenuates methamphetamine-induced inhibition of proliferation of adult rat hippocampal progenitor cells in vitro
被引:40
作者:
Ekthuwapranee, Kasima
[1
]
Sotthibundhu, Areechun
[2
,3
]
Govitrapong, Piyarat
[1
,2
,3
]
机构:
[1] Mahidol Univ, Inst Mol Biosci, Res Ctr Neurosci, Nakhon Pathom 73170, Thailand
[2] Mahidol Univ, Ctr Neurosci, Fac Sci, Nakhon Pathom, Thailand
[3] Mahidol Univ, Dept Pharmacol, Fac Sci, Nakhon Pathom, Thailand
关键词:
adult neurogenesis;
hippocampus;
melatonin;
methamphetamine;
N-methyl-d-aspartate receptor;
proliferation;
SPATIAL MEMORY;
COGNITIVE PERFORMANCE;
NEURAL PROGENITORS;
RECOGNITION MEMORY;
CYCLE ARREST;
NEUROGENESIS;
NMDA;
RECEPTORS;
NEURONS;
DIFFERENTIATION;
D O I:
10.1111/jpi.12225
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
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 500m 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 inhibitorp21(CIP1) (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 NR2A (79.6%) and NR2B (126.7%) and Ca2+/calmodulin-dependent protein kinase II (CAMKII) (74.0%). In addition, pretreatment with 1m 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.
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页码:418 / 428
页数:11
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