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Updated: Jul 19, 2026
Photobiomodulation Under Electroencephalographic Controls of Sleep for Stimulation of Lymphatic Removal of Toxins from Mouse Brain
Published on: June 28, 2024
Melatonin treatment in old mice enables a more youthful response to LPS in the brain
V M Perreau1, S C Bondy, C W Cotman
1Institute for Brain Aging and Dementia, USA.
Abstract:
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.
Insights
Dietary melatonin supplementation in aged mice shifted their central nervous system gene expression profile following an inflammatory challenge, making it resemble that of younger mice. This suggests melatonin may mitigate age-related immune changes.
Area of Science:
- Neuroimmunology
- Aging Research
- Molecular Biology
Background:
- Melatonin influences immune and inflammatory gene expression.
- Age-related decline in melatonin may contribute to immune system changes.
- Investigating melatonin's potential to counteract age-related immune alterations is crucial.
Purpose of the Study:
- To determine if dietary melatonin modifies age-related gene expression changes in the mouse central nervous system (CNS) during an inflammatory response.
- To assess melatonin's effect on the CNS's response to lipopolysaccharide (LPS)-induced inflammation in aged mice.
Main Methods:
- CB6F1 male mice of different ages were fed melatonin or a control diet.
- Animals were challenged with lipopolysaccharide (LPS) to induce inflammation.
- Messenger RNA (mRNA) expression in the brain was analyzed using oligonucleotide microarrays.
Main Results:
- Melatonin treatment significantly altered the gene expression response in older mice challenged with LPS.
- The gene expression profile in melatonin-treated aged mice more closely resembled that of young, LPS-challenged mice.
- Melatonin induced a shift towards a more youthful mRNA expression profile in the CNS of aged mice.
Conclusions:
- Dietary melatonin supplementation can significantly modify the CNS response to inflammatory challenges in aged mice.
- Melatonin treatment promotes a more youthful gene expression pattern in the aging brain, potentially mitigating age-related immune dysregulation.
