Publication: Melatonin pretreatment prevented the effect of dexamethasone negative alterations on behavior and hippocampal neurogenesis in the mouse brain
Issued Date
2014-02-28
Resource Type
Language
eng
Rights
Mahidol University
Rights Holder(s)
Elsevier
Bibliographic Citation
Molecular Biology. Vol.143, (2014), 72-80
Suggested Citation
Nootchanart Ruksee, Walaiporn Tongjaroenbuangam, Thanutchaporn Mahanam, Piyarat Govitrapong Melatonin pretreatment prevented the effect of dexamethasone negative alterations on behavior and hippocampal neurogenesis in the mouse brain. Molecular Biology. Vol.143, (2014), 72-80. doi:10.1016/j.jsbmb.2014.02.011 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/7713
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Melatonin pretreatment prevented the effect of dexamethasone negative alterations on behavior and hippocampal neurogenesis in the mouse brain
Abstract
Glucocorticoids play various physiological functions via the glucocorticoid receptor (GR). Glucocorticoid
is associated with the pathophysiology of depression. Dexamethasone (DEX), a synthetic GR agonist,
has a greater affinity for GR than the mineralocorticoid receptor (MR) in the hippocampus of pigs and
may mimic the effects of GR possession. DEX decreases neurogenesis and induces damage to hippocampal
neurons that is associated with depressive-like behavior. Melatonin, a hormone mainly synthesized
in the pineal gland, is a potent free radical scavenger and antioxidant. Melatonin alters noradrenergic
transmission in depressed patients. It may be interesting to further explore the mechanism of melatonin
that is associated with the role of stress as a key factor to precipitate depression and as a factor
altering neurogenesis. In this study, we assessed the capability of melatonin to protect the hippocampus
of mouse brains to counteract the effects of chronic DEX treatment for 21 days on depressive-like
behavior and neurogenesis. Our results revealed that chronic administration of DEX induced depressivelike
behavior and that this could be reversed by pretreatment with melatonin. Moreover, the number
of 5-bromo-2-deoxyuridine (BrdU)-immunopositive cells and doublecortin (DCX; the neuronal-specific
marker) protein levels were significantly reduced in the DEX-treated mice. Pretreatment with melatonin
was found to renew BrdU and DCX expression in the dentate gyrus. Furthermore, pretreatment withmelatonin
prevented DEX-induced reductions in GR and an extracellular-signal-regulated kinase (ERK1/2) in
the hippocampal area. Melatonin may protect hippocampal neurons from damage and reverse neurogenesis
after chronic DEX by activating brain-derived neurotrophic (BDNF) and ERK1/2 cascades. These
results revealed that melatonin pretreatment prevented the reduction of cell proliferation, immature
neuron precursor cells, and GR and ERK1/2 expression. This finding indicates that melatonin attenuates
the DEX-induced depressive-like behavior, supporting the notion that melatonin possesses anti-stress
and neurogenic actions.