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Melatonin improves d ‐galactose‐induced aging effects on behavior, neurogenesis, and lipid peroxidation in the mouse dentate gyrus via increasing pCREB expression
Author(s) -
Yoo Dae Young,
Kim Woosuk,
Lee Choong Hyun,
Shin Bin Na,
Nam Sung Min,
Choi Jung Hoon,
Won MooHo,
Yoon Yeo Sung,
Hwang In Koo
Publication year - 2012
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2011.00912.x
Subject(s) - dentate gyrus , neurogenesis , melatonin , lipid peroxidation , endocrinology , medicine , neuroscience , biology , chemistry , oxidative stress , hippocampus
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.