Article

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

Center for Occupational and Environmental Health, Department of Community and Environmental Medicine, University of California, Irvine, CA 92697-1825, USA.
Neurochemistry International (impact factor: 2.86). 02/2007; 50(2):336-44. DOI:10.1016/j.neuint.2006.09.001 pp.336-44
Source: PubMed

ABSTRACT The expression levels of a number of genes associated with inflammation and immune function change with advancing age. Melatonin modulates gene expression levels of several of these genes. Therefore the declining levels of melatonin associated with age may play a role in the physiological effects of aging. We used oligonucleotide microarrays to measure age-related changes in mRNA expression in the murine CNS, and to study the effect of prolonged administration of dietary melatonin upon these changes. CB6F1 male mice were fed 40 ppm melatonin for 2.1 months prior to sacrifice at age 26.5 months, and compared with both age-matched controls and young, 4.5-month-old untreated controls. Total RNA was extracted from whole brain (excluding cerebellum and brain stem) and individual samples were hybridized to Affymetrix Mouse 430-2.0 arrays. The expression of a substantial number of genes was modulated by melatonin treatment and changes in selected genes were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A subset of these genes did not change with age. Conversely, some genes modulated by age were also modulated by melatonin treatment. In general, melatonin treatment drove the expression levels of these genes closer to the expression levels detected in the younger animals. Notably, the abundance of lipocalin 2 (Lcn2) mRNA increased with age and was decreased in old animals treated with melatonin. Lcn2 is a member of the acute phase response family of proteins and its mRNA levels in the brain increase in response to inflammation. Many of the genes with expression reduced by melatonin are involved in inflammation and the immune system. This suggests that melatonin treatment may influence the inflammatory responses of old animals, driving them to resemble more closely those occurring in young animals.

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Keywords

40 ppm melatonin
 
acute phase response family
 
CB6F1 male mice
 
declining levels
 
dietary melatonin
 
expression levels
 
genes modulated
 
immune function change
 
individual samples
 
inflammatory responses
 
measure age-related changes
 
Melatonin modulates gene expression levels
 
melatonin treatment
 
mRNA expression
 
mRNA levels
 
murine CNS
 
oligonucleotide microarrays
 
physiological effects
 
quantitative reverse transcription polymerase chain reaction
 
whole brain
 

Edward H Sharman