Melatonin improves d‐galactose‐induced aging effects on behavior, neurogenesis, and lipid peroxidation in the mouse dentate gyrus via increasing pCREB expression

Abstract

Melatonin (N-acetyl-5-methoxytryptamine) has multiple functions. In this study, we investigated the effects of melatonin on memory, cell proliferation, and neuroblast differentiation in the dentate gyrus of a mouse model of D-galactose-induced aging. D-galactose was subcutaneously administered to 7-wk-old mice for 10 wk, and age-matched mice were used as controls. Seven weeks after D-galactose administration, vehicle (water) or melatonin (6 mg/L in water) was administered ad libitum to the mice for 3 wk. The administration of D-galactose significantly increased the escape latency compared with that in the control mice on days 1-3. In addition, cells in the subgranular zone and in the granule cell layer of the dentate gyrus showed severe damage (cytoplasmic condensation) in the D-galactose-treated mice. However, melatonin supplementation to these mice for 3 wk significantly ameliorated the D-galactose-induced increase in escape latency and neuronal damage compared with the vehicle-treated group. The administration of melatonin also significantly restored the D-galactose-induced reduction of proliferating cells (Ki67-positive cells) and differentiating neuroblasts (doublecortin-positive neuroblasts) in the dentate gyrus. Furthermore, the administration of melatonin significantly increased Ser133-phosphorylated cyclic AMP response element binding protein in the dentate gyrus. The administration of melatonin significantly reduced D-galactose-induced lipid peroxidation in the dentate gyrus. These results suggest that melatonin may be helpful in reducing age-related phenomena in the brain.

Adipose stem cells’ antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function

“…[1][2][3] Glycosylation is a non-enzyme reaction among free amino acid groups in collagen, as well as the oxidization induced by oxygen activation gene. However, the glycosylation induced by reaction between reducing sugar and protein is the important factor that causes body aging.…”

Effect of Capparis spinosa L. on cognitive impairment induced by D-galactosein mice via inhibition of oxidative stress

“…In order to explain the mechanism of D-galactose, many hypotheses have been put forward; one of them is that chronic systemic exposure to D-galactose increases levels of MDA and lipofuscin and also decreases GPx and SOD activities (6,41). In our study, when the Morris water maze test was applied, we observed that long-term administration of D-galactose in mice caused cognitive deficit and showed significant impairment of learning and memory ability.…”

“…When it is present at higher levels than normal, it can be converted to galactitol by galactose oxidase, resulting in the generation of oxygen-derived free radicals (6). Chronic systemic exposure to D-galactose induces aging-related changes such as corruption of spatial learning, memory loss, neurodegeneration, and diminishing activities of antioxidant enzymes and increased production of free radicals (7)(8)(9).…”

Probiotics: An Adjuvant therapy for D-Galactose induced Alzheimer's disease

“…It also induces the expression of tumor necrosis factor-alpha, interleukin-1b (IL-1b) and IL-6 [13]. DGalactose increases replicative senescence markers p16 expression and telomere shortening but reduces doublecortin (DCX) expression [14]. Therefore, D-galactose continuously stimulates low-grade inflammation, which is associated with the acceleration of aging.…”