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

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 40ppm melatonin for 2.1 months prior to sacrifice at age 26.5 months, and compared with both age-matched controls and young, 4.5-monthold 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.

Light Interference (LI) as a possible stressor altering HSP70 and its gene expression levels in brain and liver tissues of Golden Spiny Mice

“…Results of an in vitro study revealed an increase in hsp60 gene expression after the cells were treated with MLT (Bonior et al, 2005). In contrast, the results of Sharman et al (Sharman et al, 2007) showed that MLT decreased hsp70 mRNA expression in brain tissues from aged mice.…”

Does Melatonin Ameliorate Neurological Changes Associated With Alzheimer’s Disease in Ovariectomized Rat Model?

“…Martinez et al [28] reported that melatonin reduces the neuronal damage mediated by ROS. Melatonin has a powerful scavenging activity for hydroxyl and peroxyl radicals over that of both glutathione and vitamin E. Melatonin also conserves the activities of the antioxidant enzymes via enhancing gene expression of these enzymes [29]. Melatonin has a phenol group that provides a proton to detoxify hydroxyl or lipid peroxy radicals and thus can reduce lipid peroxidation induced by Al in Alzheimer's patients [30].…”

The effects of aging vs. α7 nAChR subunit deficiency on the mouse brain transcriptome: aging beats the deficiency

“…Upregulation of immune response genes was previously demonstrated in murine and human brains (Lee et al 2000;Terao et al 2002). Specifically, the expression of the complement component genes C1qa, C1qb, C1qc, and C4b was increased in aged murine's hippocampus, neocortex, cerebellum, and whole brain (Blalock et al 2003;Burger et al 2008;Prolla 2002;Rowe et al 2007;Sharman et al 2007), and C1qa and C1qb expression levels were also upregulated in normal-aged human brains (Berchtold et al 2008). Interestingly, glial cells of AD patients secreted more C1q than nondemented elderly controls (Lue et al 2001).…”

“…We generated two lists of genes that were previously detected as changed in aging brains in eight mouse or rat expression microarray experiments (Blalock et al 2003;Burger et al 2008;Cho et al 2002;Jiang et al 2001;Kadish et al 2009;Prolla 2002;Rowe et al 2007;Sharman et al 2007) and in four human experiments (Berchtold et al 2008;Erraji-Benchekroun et al 2005;Lu et al 2004;Tang et al 2009). These studies profiled different gender compositions and samples from various ages.…”

“…We compiled a list of genes that were previously reported as changed in brains of aged mice or rats (Blalock et al 2003;Burger et al 2008;Cho et al 2002;Jiang et al 2001;Kadish et al 2009;Prolla 2002;Rowe et al 2007;Sharman et al 2007;Supplementary Table 3a). Of these, 2,032 genes are represented on the Mouse Genome 430 2.0 array (by 3,942 probe sets).…”