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

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 40ppm 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 hours, 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

Stimulation of synaptosomal free radical production by fatty acids: relation to esterification and to degree of unsaturation.

The ability of three fatty acids and their respective ethyl esters, to promote generation of reactive oxygen species (ROS), was compared in a preparation of rat brain synaptosomes. Arachidonic but not palmitic or linoleic acids promoted ROS generation. Ethyl esterification of each fatty acid significantly enhanced ROS production and also levels of lipid peroxidaton. Pro-oxidant activity was enhanced by fatty acids, proportionally to their degree of unsaturation. Since ethanol consumption is known to lead to esterification of membrane lipids, this transformation may in part account for the ROS-promoting potential of alcohol