Significance of High Levels of Endogenous Melatonin in Mammalian Cerebrospinal Fluid and in the Central Nervous System

Dun-Xian      Tan; Lucien      C. Manchester; Emilio      Sanchez-Barcelo; Maria      D. Mediavilla; Russel      J. Reiter

Abstract

Levels of melatonin in mammalian circulation are well documented; however, its levels in tissues and other body fluids are yet only poorly established. It is obvious that melatonin concentrations in cerebrospinal fluid (CSF) of mammals including humans are substantially higher than those in the peripheral circulation. Evidence indicates that melatonin produced in pineal gland is directly released into third ventricle via the pineal recess. In addition, brain tissue is equipped with the synthetic machinery for melatonin production and the astrocytes and glial cells have been proven to produce melatonin. These two sources of melatonin may be responsible for its high levels in CNS. The physiological significance of the high levels of melatonin in CNS presumably is to protect neurons and glia from oxidative stress. Melatonin as a potent antioxidant has been reported to be a neuroprotector in animals and in clinical studies. It seems that long term melatonin administration which elevates CSF melatonin concentrations will retard the progression of neurodegenerative disorders, for example, Alzheimer disease.

Keywords: Melatonin, pineal gland, CNS, CSF, oxidative stress, neurodegenerative disease