Abstract
Regulation of adult hippocampal neurogenesis is influenced by circadian rhythm, affected by the manipulation of sleep, and is disturbed in animal models of affective disorders. These observations and the link between dysregulation of the circadian production of melatonin and neuropsychiatric disorders prompted us to investigate the potential role of melatonin in controlling adult hippocampal neurogenesis. In vitro, melatonin increased the number of new neurons derived from adult hippocampal neural precursor cells in vitro by promoting cell survival. This effect was partially dependent on the activation of melatonin receptors as it could be blocked by the application of receptor antagonist luzindole. There was no effect of melatonin on cell proliferation. Similarly, in the dentate gyrus of adult C57BL/6 mice in vivo, exogenous melatonin (8 mg/kg) also increased the survival of neuronal progenitor cells and post-mitotic immature neurons. Melatonin did not affect precursor cell proliferation in vivo and also did not influence neuronal and glial cell maturation. Moreover, melatonin showed antidepressant-like effects in the Porsolt forced swim test. These results indicate that melatonin through its receptor can modulate the survival of newborn neurons in the adult hippocampus, making it the first known exogenously applicable substance with such specificity
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Acknowledgements
This work was supported by VolkswagenStiftung. GBK was supported by CONACYT (Grant no. 46593-M). We thank Sebastian Mirochnic for helpful discussions, and Ruth Zarmsftorff, Signe Knespel, Patricia Chimal-Cortes for technical assistance.
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No pharmaceutical company was involved in funding the present research. Gerd Kempermann has received compensation over the last 3 years from Glaxo Smith Kline, Novartis Foundation, and Tecan as honorarium for lectures. Gloria Benitez-King, Gerardo Ramirez-Rodriguez, Harish Babu, and Friederike Klempin have received, except for income received from my primary employer, no financial support or compensation from any individual or corporate entity for research or professional services in any of the previous 3 years, and no financial holdings that could be perceived as constituting a potential conflict of interest.
Supplementary Information accompanies the paper on the Neuropsychopharmacology website (http://www.nature.com/npp)
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Ramírez-Rodríguez, G., Klempin, F., Babu, H. et al. Melatonin Modulates Cell Survival of New Neurons in the Hippocampus of Adult Mice. Neuropsychopharmacol 34, 2180–2191 (2009). https://doi.org/10.1038/npp.2009.46
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DOI: https://doi.org/10.1038/npp.2009.46
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