Melatonin, a Neuroprotective Agent: Relevance for Stress-Induced Neuropsychiatric Disorders

  • Piyarat Govitrapong
  • Kasima Ekthuwapranee
  • Nootchanart Ruksee
  • Parichart Boontem


Neuropsychiatric disorders commonly refer to psychiatric diseases caused by brain disorders. The main components of neuropsychiatric symptoms are cognitive impairment, depression, anxiety, paranoid-hallucinatory states, and behavioral and personality changes. Chronic stress is a major factor in depressive disorders. Dysregulation of hypothalamo-pituitary-adrenal axis is a common characteristic of depression. The cellular and molecular mechanisms underlying the role of stress in inducing these symptoms will be discussed. Melatonin, a hormone mainly secreted in the pineal gland, has pleiotropic neuropsychiatric actions mediated via several signaling pathways. It significantly prevented stress-induced memory deficits and depressive behavior; decreased the expressions of brain-derived neurotrophic factor (BDNF), glucocorticoid receptor (GR), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and synaptophysin; and reduced bromodeoxyuridine (BrdU)-labeled proliferating cells, doublecortin, and neurogenesis. The neurogenesis hypothesis of depression will be discussed, and the role of melatonin in this hypothesis will be presented. According to the novel function of new neurons in the stress response regulation, it is possible that melatonin can be used as a therapeutic agent to protect neurons and prevent the decrease of neurogenesis, which in turn reverses stress-induced depression.


Glucocorticoid Receptor Dentate Gyrus Hippocampal Neurogenesis Melatonin Receptor Chronic Unpredictable Stress 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The financial support from the Thailand Research Fund (grant No.DPG5780001) and a Mahidol University Research Grant to PG is gratefully acknowledged.


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Copyright information

© Springer India 2016

Authors and Affiliations

  • Piyarat Govitrapong
    • 1
    • 2
  • Kasima Ekthuwapranee
    • 1
  • Nootchanart Ruksee
    • 1
    • 3
  • Parichart Boontem
    • 1
  1. 1.Research Center for Neuroscience, Institute of Molecular BiosciencesMahidol UniversitySalayaThailand
  2. 2.Center for Neuroscience and Department of Pharmacology, Faculty of ScienceMahidol UniversitySalayaThailand
  3. 3.National Institute for Child and Family DevelopmentMahidol UniversitySalayaThailand

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