title: Melatonin enhances adult rat hippocampal progenitor cell proliferation via ERK signaling pathway through melatonin receptor.
abstract: Melatonin, a neurohormone secreted mainly by the pineal gland, has a variety of physiological functions and neuroprotective effects. Previous studies have shown that melatonin could stimulate the proliferation of neural stem/progenitor cells (NS/PCs). Recent studies reported that the activities of mitogen-activated protein kinase (MAPK) of neural stem cells (NSCs) changed in response to the proliferative effect of melatonin. Therefore, the aim of the present study was to explore the proliferative mechanism mediated by melatonin on the adult rat hippocampal NS/PCs. Treatment with melatonin significantly increased the number of neurospheres in a concentration-dependent manner and up-regulated nestin protein. Pretreatment with luzindole, a melatonin receptor antagonist, and PD98059, a mitogen-activated protein kinase kinase (MEK) inhibitor, prevented the increase in the number of neurospheres formed by the activation of melatonin. The levels of phospho-c-Raf and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) increased when treated with melatonin. Pretreatment with luzindole or PD98059 prevented the melatonin-induced increase in these signaling molecules. The present results showed that melatonin could induce NS/PCs to proliferate by increasing phosphorylation of ERK1/2 and c-Raf through melatonin receptor. These results provide further evidence for a role of melatonin in promoting neurogenesis, adding to the remarkably pleiotropic nature of this neurohormone. This intrinsic modulator deserves further investigation to better understand its physiological and therapeutic implication.
authors: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors: C
authors: C
authors: Tocharus
authors: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors: Y
authors: Y
authors: Puriboriboon
authors: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors: T
authors: T
authors: Junmanee
authors: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors: J
authors: J
authors: Tocharus
authors: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom 73170, Thailand.
authors: K
authors: K
authors: Ekthuwapranee
authors: Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakornpathom 73170, Thailand; Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok 10400, Thailand. Electronic address: piyarat.gov@mahidol.ac.th.
authors: P
authors: P
authors: Govitrapong
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology; D000375:Aging; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008550:Melatonin / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044094:Receptors, Melatonin / Q000378:metabolism*
chemical_list: D044094:Receptors, Melatonin; D008550:Melatonin
keywords: MAPK; adult hippocampal NS/PC; melatonin; neurosphere; proliferation