Melatonin, metals, and gene expression: implications in aging and neurodegenerative disorders.
Melatonin is a hormone secreted by the pineal gland, mostly in the dark period of the light/dark cycle, with corresponding fluctuations reflected in the plasma melatonin levels. This hormone plays a critical role in the regulation of various neural and endocrine processes that are synchronized with daily change in photoperiod. Abnormal melatonin levels are associated with metabolic disturbances and other disorders. Melatonin potentially plays an important role in aging, prolongation of life span, and health in the aged individual. It may exert a beneficial action on neurodegenerative conditions in those with debilitating diseases. It interacts with metals and, in some cases, neutralizes their toxic effects. Levels of melatonin decrease with aging in mice. Its dietary supplementation has recently been shown to result in a significant rise in levels of endogenous melatonin in serum as well as all other tissue samples tested. The effects of dietary melatonin have been studied in the brain of mice with regard to nitric oxide synthase, synaptic proteins, and amyloid beta peptides (Abeta), which are involved in amyloid deposition and plaque formation in Alzheimer's disease (AD). Melatonin supplementation has no significant effect on cerebral cortical levels of nitric oxide synthase or synaptic proteins, such as synaptophysin and SNAP-25. Notably, however, elevated brain melatonin levels resulted in a significant reduction in levels of toxic cortical Abeta of both 40- and 42-amino-acid forms. Taken together, these results suggest that dietary melatonin supplementation may slow the neurodegenerative changes associated with brain aging and that the depletion of melatonin in the brain of aging mice may, in part, account for this adverse change.
Lahiri
Debomoy K
DK
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, 46202, USA.dlahiri@iupui.edu
Chen
Demao
D
Lahiri
Preeti
P
Rogers
Jack T
JT
Greig
Nigel H
NH
Bondy
Stephen
S
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D019587:Dietary Supplements; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008550:Melatonin / Q000378:metabolism* / Q000627:therapeutic use; D008670:Metals / Q000633:toxicity; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*
D008670:Metals; D008550:Melatonin