Dietary supplementation with melatonin reduces levels of amyloid beta‐peptides in the murine cerebral cortex

Abstract

Melatonin levels decrease with aging in mice. Dietary supplementation with melatonin has recently been shown to result in a significant rise in levels of endogenous melatonin in the serum and all other tissue samples tested. Herein, the effects of dietary melatonin on brain levels of nitric oxide synthase, synaptic proteins and amyloid beta-peptides (Abeta) were determined in mice. Melatonin supplementation did not significantly change cerebral cortical levels of nitric oxide synthase or synaptic proteins such as synaptophysin and SNAP-25. Increased brain melatonin concentrations however, led to a significant reduction in levels of toxic cortical Abeta of both short and long forms which are involved in amyloid depositions and plaque formation in Alzheimer's diseases. Thus, melatonin supplementation may retard neurodegenerative changes associated with brain aging. Depletion of melatonin in the brain of aging mice may in part account for this adverse change.

Aluminum and copper in drinking water enhance inflammatory or oxidative events specifically in the brain

“…APP was measured by Western blotting technique as previously described (Lahiri et al, 2004). Briefly, 30 Ag of total brain protein was separated on a 12% polyacrylamide gel containing sodium dodecyl sulfate (SDS-PAGE).…”

Effects of melatonin and age on gene expression in mouse CNS using microarray analysis

“…The pulsatile nocturnal peak level of melatonin decreases with age in rats (Pang et al, 1990), mice (Lahiri et al, 2004a) and humans (Tozawa et al, 2003), and is predicted to be involved in regulation of sleep, which is commonly disturbed in the elderly (Foley et al, 1995).…”

“…Melatonin receptor mRNA is detected in a number of areas within the CNS, including the pituitary pars tuberalis, the suprachiasmatic nucleus of the hypothalamus (von Gall et al, 2002), the hippocampus and cerebellum (Al-Ghoul et al, 1998). In the rat, melatonin receptor density decreases with age in the hypothalamus and the hippocampus (Laudon et al, 1998), and melatonin supplementation increases both melatonin levels (Menedez-Pelaez et al, 1993;Lahiri et al, 2004a) and melatonin binding (OakninBendahan et al, 1995) in the brains of older animals. In the current study we sought to gain a better understanding of melatonin's possible neuroprotective mechanisms by comparing the age-related CNS gene expression patterns of young and old mice and old mice receiving dietary melatonin.…”

Role of Nitric Oxide in Neurodegeneration and Vulnerability of Neuronal Cells to Nitric Oxide Metabolites and Reactive Oxygen Species

“…Melatonin hormone, a well-characterized antioxidant, could play an important protective role in aging and AD based on cellular and animal studies [41,42]. Inhibition of NO production may be a further means whereby melatonin reduces oxidative damage under conditions, such as in ischemia/reperfusion and sepsis, where NO seems to be important in terms of the resulting damage [43].…”

“…Inhibition of NO production may be a further means whereby melatonin reduces oxidative damage under conditions, such as in ischemia/reperfusion and sepsis, where NO seems to be important in terms of the resulting damage [43]. Previously, we have shown that melatonin can promote neuronal differentiation [41,44]. We have additionally explored whether the treatment of cultured cells with melatonin can reduce the release of free radicals and other ROS.…”