Melatonin ameliorates cuprizone‐induced reduction of hippocampal neurogenesis, brain‐derived neurotrophic factor, and phosphorylation of cyclic AMP response element‐binding protein in the mouse dentate gyrus

Brain and Behavior

Dae Young Yoo¹  Sung Min Nam²  Jong Whi Kim³  Kyu Ri Hahn³  Woosuk Kim³  Hyo Young Jung³  In Koo Hwang³  Yeo Sung Yoon³  Dae Won Kim⁴  Hyun Jung Kwon⁴  Joon Ha Park⁵  Moo‐Ho Won⁶ 

[1] Department of Anatomy College of Medicine Soonchunhyang University Cheonan South Korea;Department of Anatomy College of Veterinary Medicine Konkuk University Seoul South Korea;Department of Anatomy and Cell Biology College of Veterinary Medicine, and Research Institute for Veterinary Science Seoul National University Seoul South Korea;Department of Biochemistry and Molecular Biology College of Dentistry Research Institute of Oral Sciences Gangneung‐Wonju National University Gangneung South Korea;Department of Biomedical Science and Research Institute for Bioscience and Biotechnology Hallym University Chuncheon Korea;Department of Neurobiology School of Medicine Kangwon National University Chuncheon Korea;

关键词: C57BL/6 mouse;    cuprizone;    hippocampus;    melatonin;    neurogenesis;   

DOI  :  10.1002/brb3.1388

来源: DOAJ

【 摘 要 】

Abstract Introduction The aim of this study was to investigate the effects of cuprizone on adult hippocampal neurogenesis in naïve mice. Additionally, we also studied how melatonin affects the neuronal degeneration induced by cuprizone. Methods Eight‐week‐old male C57BL/6J mice were randomly divided into three groups: (a) the control group, (b) the group treated with cuprizone only, and (c) the group treated with both cuprizone and melatonin. Cuprizone was administered with food at 0.2% ad libitum for 6 weeks. Melatonin was also administered with tap water at 6 g/L ad libitum for 6 weeks; the animals were then euthanized for immunohistochemistry with Ki67, doublecortin (DCX), glucose transporter 3 (GLUT3), and phosphorylation of cyclic adenosine monophosphate (AMP) response element binding (pCREB); double immunofluorescence of neuronal nuclei (NeuN) and myelin basic protein (MBP); and Western blot analysis of brain‐derived neurotrophic factor (BDNF) expression to reveal the effects of cuprizone and melatonin on cell damage and hippocampal neurogenesis. Results Administration of cuprizone significantly decreased the number of differentiating (DCX‐positive) neuroblasts and proliferating (Ki67‐positive) cells in the dentate gyrus. Moreover, cuprizone administration decreased glucose utilization (GLUT3‐positive cells) and cell transcription (pCREB‐positive cells and BDNF protein expression) in the dentate gyrus. Administration of melatonin ameliorated the cuprizone‐induced reduction of differentiating neuroblasts and proliferating cells, glucose utilization, and cell transcription. Conclusion The results of the study suggest that cuprizone treatment disrupts hippocampal neurogenesis in the dentate gyrus by reducing BDNF levels and decreasing the phosphorylation of CREB. These effects were ameliorated by melatonin treatment.

【 授权许可】

Unknown