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.
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The mechanisms through which melatonin can exert neuroprotective and cognitive-enhancing effects include anti-inflammatory and antioxidant properties, as well as enhanced neuroplasticity and neurogenesis.
“The mechanisms through which melatonin can exert neuroprotective and cognitive-enhancing effects include anti-inflammatory and antioxidant properties, as well as enhanced neuroplasticity and neurogenesis [142].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [142]
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- Authors
- Tocharus, C., Puriboriboon, Y., Junmanee, T., Tocharus, J., Ekthuwapranee, K., & Govitrapong, P.
- Affiliations
- Chiang Mai University (TH)
- Mahidol University (TH)
- Corresponding author
- Govitrapong, P.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 275
- Pages
- 314-321
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2009218904
- Cited by
- 96
- References
- 32
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 11 · 2016: 16 · 2015: 7 · 2014: 2
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Thailand Research Fund (DPG5780001)
- Mahidol University
- Faculty of Medicine Research Fund, Chiang Mai University
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- melatonin, hippocampal progenitor cells, neural stem/progenitor cells, cell proliferation, ERK signaling, Raf-1, melatonin receptors, MAPK signaling, neurogenesis, neurospheres, nestin, luzindole, PD98059
- MeSH terms
- Aging, Animals, Hippocampus, Melatonin, Blotting, Western, Rats, Sprague-Dawley, MAP Kinase Signaling System, Receptors, Melatonin, Cell Proliferation, Rats, Adult Stem Cells, Neurogenesis, Neural Stem Cells
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