Dietary melatonin selectively reverses age-related changes in cortical cytokine mRNA levels, and their responses to an inflammatory stimulus

Sharman, Kaizhi G.; Sharman, Edward; Yang, Ellen; Bondy, Stephen C.

doi:10.1016/s0197-4580(01)00329-3

Cited by 44 publications

(52 citation statements)

References 52 publications

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“…All of these may be attenuated by chronic treatment with dietary melatonin [79][80][81][82][83]. Melatonin can restore the ability of the aging brain to respond to an inflammatory stimulus [19], and this is in concordance with reports of favorable effects of melatonin on the circulating immune system (described earlier). However, melatonin can also reduce excess immune responsivity (discussed in a later section).…”

Section: Specific Effects Of Melatonin On Events Relating To Brain Agingsupporting

confidence: 83%

“…Several indices of immune activity in the nervous system are persistently elevated with age despite the absence of provocative stimuli [17][18][19][20]. The microglia of the brain can act as the brain's macrophages, and their level of activation is markedly increased in the white matter of the brains of aged rats [21] and primates [22].…”

Section: Inflammation and The Aged Brainmentioning

confidence: 99%

“…However, elevated basal inflammatory activity in aged animals is not accompanied by keener immune surveillance and an improved ability to respond to an inflammatory stimulus of exogenous origin. On the contrary, the ability of the intrinsic immune system within the CNS to react to a material such as lipopolysaccharide is considerably diminished in the elderly mouse [19]. Such a dampening of the ability of immune defenses to detect relevant extraneous stimuli implies an impaired ability to mount an effective response to pathogens.…”

Section: Inflammation and The Aged Brainmentioning

confidence: 99%

“…Melatonin may be of specific value to the CNS where it is able to induce antioxidant genes [57]. This may account for its ability to attenuate lipopolysaccharide (LPS)-induced inflammatory responses [19,58,59] and to ameliorate the indices of anxiety induced by LPS [60]. β-Amyloid-induced interleukin secretion and production of reactive oxygen species are also suppressed by melatonin [61,62].…”

Section: The Potential Retardation Of Brain Aging By Melatoninmentioning

confidence: 99%

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Melatonin, Oxidative Stress, and the Aging Brain

Bondy

Sharman

2010

Aging and Age-Related Disorders

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The changes associated with brain aging are discussed with emphasis on altered oxidative and inflammatory events and on mitochondrial dysfunction. Many of these changes are exacerbated in a variety of age-related neurologic diseases. This commonality has led to the idea that similar therapeutic approaches may be used in the treatment of several apparently unrelated neurodegenerative disorders. When aspects of these diseases are modeled in experimental animals and cell lines, the application of melatonin has been reported to be advantageous. The means by which melatonin can be protective probably is mediated by way of activation of melatonin receptors, of which several subtypes can be identified. This can initiate a sequence of intracellular signaling events and by activation of transcription factors lead to altered gene expression. The culmination of this cascade can lead to increased levels of antioxidant enzymes and depressed levels of inflammation. Melatonin may be useful both in the retardation of nonpathologic brain aging and in the amelioration of chronic brain disease associated with aging. The inexpensive nature and ready availability of melatonin together with its very low toxicity reinforce the need to place the beneficial properties of this agent on a firmer basis.

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Section: Specific Effects Of Melatonin On Events Relating To Brain Agingsupporting

confidence: 83%

Section: Inflammation and The Aged Brainmentioning

confidence: 99%

Section: Inflammation and The Aged Brainmentioning

confidence: 99%

Section: The Potential Retardation Of Brain Aging By Melatoninmentioning

confidence: 99%

See 2 more Smart Citations

Melatonin, Oxidative Stress, and the Aging Brain

Bondy

Sharman

2010

Aging and Age-Related Disorders

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“…In addition rat microglia also increase basal gene expression of IL-1α, IL-1β and IL-6 cytokines with aging (Yu et al, 2002). We have previously reported the influence of low doses of melatonin in mouse brain on the effect of LPS upon genes relating to immune function (Sharman et al, 2002;Bondy et al, 2005). The current study examined the global changes of cortical gene expression after acute LPS treatment following extended administration of dietary melatonin.…”

Section: Introductionmentioning

confidence: 86%

Melatonin treatment in old mice enables a more youthful response to LPS in the brain

Perreau

Bondy

Cotman

et al. 2007

Journal of Neuroimmunology

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Melatonin modulates the expression of a number of genes related to inflammation and immunity. Declining levels of melatonin with age may thus relate to some of the changes in immune function that occur with age. mRNA expression levels in murine CNS were measured using oligonucleotide microarrays in order to determine whether a dietary melatonin supplement may modify age-related changes in the response to an inflammatory challenge. CB6F1 male mice were fed 40-ppm melatonin for 9 weeks prior to sacrifice at 26.5 months of age, and compared with age-matched untreated controls and 4.5-month-old controls. A subset of both young and old animals was injected i.p. with lipopolysaccharide (LPS). After 3 h, total RNA was extracted from whole brain (excluding brain stem and cerebellum), and individual samples were hybridized to Affymetrix Mouse 430-2.0 arrays. Data were analyzed in Dchip and GeneSpring. Melatonin treatment markedly altered the response in gene expression of older animals subjected to an LPS challenge. These changes in general, caused the response to more closely resemble that of young animals subjected to the same LPS challenge. Thus melatonin treatment effects a major shift in the response of the CNS to an inflammatory challenge, causing a transition to a more youthful mRNA expression profile.

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Chronic exposure to aluminum in drinking water increases inflammatory parameters selectively in the brain

Campbell

Becaria

Lahiri

et al. 2004

J of Neuroscience Research

155

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A link between aluminum (Al) exposure and age-related neurological disorders has long been proposed. Although the exact mechanism by which the metal may influence disease processes is unknown, there is evidence that exposure to Al causes an increase in both oxidative stress and inflammatory events. These processes have also been suggested to play a role in Alzheimer's disease (AD), and exposure to the metal may contribute to the disorder by potentiating these events. Al lactate (0.01, 0.1, and 1 mM) in drinking water for 10 weeks increased inflammatory processes in the brains of mice. The lowest of these levels is in the range found to increase the prevalence of AD in regions where the concentrations of the metal are elevated in residential drinking water (Flaten [2001] Brain Res. Bull. 55:187-196). Nuclear factor-kappaB as well as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1alpha (IL-1alpha) levels were increased in the brains of treated animals. The mRNA for TNF-alpha was also up-regulated following treatment. Enhancement of glial fibrillary acidic protein levels and reactive microglia was seen in the striatum of Al-treated animals. The level of amyloid beta (Abeta40) was not significantly altered in the brains of exposed animals. Insofar as no parallel changes were observed in the serum or liver of treated animals, the proinflammatory effects of the metal may be selective to the brain. Al exposure may not be sufficient to cause abnormal production of the principal component of senile plaques directly but does exacerbate underlying events associated with brain aging and thus could contribute to progression of neurodegeneration.

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Dietary melatonin selectively reverses age-related changes in cortical cytokine mRNA levels, and their responses to an inflammatory stimulus

Cited by 44 publications

References 52 publications

Melatonin, Oxidative Stress, and the Aging Brain

Melatonin, Oxidative Stress, and the Aging Brain

Melatonin treatment in old mice enables a more youthful response to LPS in the brain

Chronic exposure to aluminum in drinking water increases inflammatory parameters selectively in the brain

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