Melatonin potentiates running wheel-induced neurogenesis in the dentate gyrus of adult C3H/HeN mice hippocampus

Authors

  • Jiabei Liu,

    1. Department of Pharmacology & Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA
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  • Kathleen C. Somera-Molina,

    1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    Current affiliation:
    1. Acorda Therapeutics Inc., Hawthorne, NY, USA
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  • Randall L. Hudson,

    1. Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA
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  • Margarita L. Dubocovich

    Corresponding author
    1. Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    • Department of Pharmacology & Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA
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Address reprint requests to Margarita L. Dubocovich,

Department of Pharmacology & Toxicology,

School of Medicine and Biomedical Sciences, 3435 Main Street (Farber Hall 102), University at Buffalo (SUNY), Buffalo, 14214, USA.

E-mail: mdubo@buffalo.edu

Abstract

This study assessed the role of melatonin in modulating running wheel(RW)-induced hippocampal neurogenesis in adult C3H/HeN mice. Chronic melatonin (0.02 mg/mL, oral for 12 days) treatment did not affect cell proliferation or cell survival determined by the number of BrdU-positive cells in dentate gyrus of mice with access to fixed wheel (FW). RW activity significantly increased cell proliferation [RW (n = 8) versus FW (n = 6): dorsal, 199 ± 18 versus 125 ± 12, P < 0.01; ventral, 211 ± 15 versus 123 ± 13, P < 0.01] and newborn cell survival [RW (n = 7) versus FW (n = 8): dorsal, 45 ± 8.5 versus 15 ± 1.8, P < 0.01; ventral, 48 ± 8.1 versus 15 ± 1.4)] in the dorsal and ventral dentate gyrus. Oral melatonin treatment further potentiated RW activity-induced cell survival in both areas of the dentate gyrus [melatonin (n = 10) versus vehicle (n = 7): dorsal, 63 ± 5.4 versus 45 ± 8.5 P < 0.05; ventral, 75 ± 7.9 versus 48 ± 8.1, P < 0.01] and neurogenesis [melatonin (n = 8) versus vehicle (n = 8): dorsal, 46 ± 3.4, versus 34 ± 4.5, P < 0.05; ventral, 41 ± 3.4 versus 25 ± 2.4, P < 0.01]. We conclude that melatonin potentiates RW-induced hippocampal neurogenesis by enhancing neuronal survival suggesting that the combination of physical exercise and melatonin may be an effective treatment for diseases affecting the hippocampus neurogenesis.

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