Comparing the Effects of Melatonin with Caloric Restriction in the Hippocampus of Aging Mice: Involvement of Sirtuin1 an
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ORIGINAL PAPER
Comparing the Effects of Melatonin with Caloric Restriction in the Hippocampus of Aging Mice: Involvement of Sirtuin1 and the FOXOs Pathway Anorut Jenwitheesuk1 · Seongjoon Park2 · Prapimpun Wongchitrat3 · Jiraporn Tocharus4 · Sujira Mukda1 · Isao Shimokawa2 · Piyarat Govitrapong1,5,6
Received: 23 April 2017 / Revised: 25 July 2017 / Accepted: 26 July 2017 © Springer Science+Business Media, LLC 2017
Abstract It has been suggested that age-related neurodegeneration might be associated with neuropeptide Y (NPY); sirtuin1 (SIRT1) and forkhead box transcription factors O subfamily (FOXOs) pathways. Melatonin, a hormone mainly secreted by the pineal gland, is another anti-aging agent associated with the SIRT1-FOXOs pathway. This study aimed to compare the effects of melatonin (Mel) and caloric restriction (CR) on the expression of Sirt1, FoxO1, FoxO3a and FOXOs target genes in the aging mouse hippocampus. Neuropeptide Y-knockout (NpyKO) and wild-type (WT) male mice aged 19 months were previously treated either with food ad libitum or CR for 16 months. WT old animals were divided into four groups: Isao Shimokawa and Piyarat Govitrapong have contributed equally to this work. * Isao Shimokawa shimo@nagasaki‑u.ac.jp * Piyarat Govitrapong [email protected]; [email protected] 1
Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Salaya, Thailand
2
Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, 1‑12‑4, Sakamoto, Nagasaki 852‑8523, Japan
3
Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Salaya, Nakon Pathom 73170, Thailand
4
Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
5
Center for Neuroscience and Department of Pharmacology, Faculty of Science, Mahidol University, Salaya, Thailand
6
Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Kamphaeng Phet 6 Road, Lak Si, Bangkok 10210, Thailand
control, CR, Mel and CR+Mel treated groups. The Mel and CR+Mel were treated with melatonin 10 mg/kg, daily, subcutaneously for 7 consecutive days. Mel treatment upregulated the mRNA expression of Sirt1, FOXOs (FoxO1 and FoxO3a) target genes that regulated the cell cycle [e.g., cyclin-dependent kinase inhibitor 1B (p27)], Wingless and INT-1 (Wnt1) and inducible signaling pathway protein 1 (Wisp1) in the aged mouse hippocampus. CR treatment also showed the similar actions. However, the mRNA expression of Sirt1, FoxO1, FoxO3a, p27 or Wisp1 did not alter in the CR+Mel group when compared with CR or Mel group. Melatonin could not produce any additive effect on the CR treatment group, suggesting that both treatments mimicked the effect, possibly via the same pathway. NPY which mediates physiological adaptations to energy deficits is an essential link between CR and longevity in mice. In order to focus on the role of Npy in mediating the effects of melatonin, the gene expression between NpyKO and WT male mice
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