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Melatonin attenuates scopolamine-induced cognitive impairment via protecting against demyelination through BDNF-TrkB signaling in the mouse dentate gyrus.

Abstract
Animal models of scopolamine-induced amnesia are widely used to study underlying mechanisms and treatment of cognitive impairment in neurodegenerative diseases such as Alzheimer's disease (AD). Previous studies have identified that melatonin improves cognitive dysfunction in animal models. In this study, using a mouse model of scopolamine-induced amnesia, we assessed spatial and short-term memory functions for 4 weeks, investigated the expression of myelin-basic protein (MBP) in the dentate gyrus, and examined whether melatonin and scopolamine cotreatment could keep cognitive function and MBP expression. In addition, to study functions of melatonin for keeping cognitive function and MBP expression, we examined expressions of brain-derived neurotrophic factor (BDNF) and tropomycin receptor kinase B (TrkB) in the mouse dentate gyrus. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally treated for 2 and 4 weeks. Two and 4 weeks after scopolamine treatment, mice showed significant cognitive impairment; however, melatonin and scopolamine cotreatment recovered cognitive impairment. Two and 4 weeks of scopolamine treatment, the density of MBP immunoreactive myelinated nerve fibers was significantly decreased in the dentate gyrus; however, scopolamine and melatonin cotreatment significantly increased the scopolamine-induced reduction of MBP expression in the dentate gyrus. Furthermore, the cotreatment of scopolamine and melatonin significantly increased the scopolamine-induced decrease of BDNF and TrKB immunoreactivity in the dentate gyrus. Taken together, our results indicate that melatonin treatment exerts anti-amnesic effect and restores the scopolamine-induced reduction of MBP expression through increasing BDNF and TrkB expressions in the mouse dentate gyrus.
AuthorsBai Hui Chen, Joon Ha Park, Tae-Kyeong Lee, Minah Song, Hyunjung Kim, Jae Chul Lee, Young-Myeong Kim, Choong-Hyun Lee, In Koo Hwang, Il Jun Kang, Bing Chun Yan, Moo-Ho Won, Ji Hyeon Ahn
JournalChemico-biological interactions (Chem Biol Interact) Vol. 285 Pg. 8-13 (Apr 01 2018) ISSN: 1872-7786 [Electronic] Ireland
PMID29476728 (Publication Type: Journal Article)
CopyrightCopyright © 2018 Elsevier B.V. All rights reserved.
Chemical References
  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • Myelin Basic Protein
  • BDNF protein, human
  • Scopolamine
  • Receptor, trkB
  • tropomyosin-related kinase-B, human
  • Melatonin
Topics
  • Animals
  • Antioxidants (pharmacology, therapeutic use)
  • Brain-Derived Neurotrophic Factor (metabolism)
  • Cognition (drug effects)
  • Cognitive Dysfunction (chemically induced, drug therapy)
  • Demyelinating Diseases (prevention & control)
  • Dentate Gyrus (drug effects, metabolism)
  • Gene Expression Regulation (drug effects)
  • Male
  • Melatonin (pharmacology, therapeutic use)
  • Membrane Glycoproteins (metabolism)
  • Mice
  • Myelin Basic Protein (genetics)
  • Receptor, trkB (metabolism)
  • Scopolamine
  • Signal Transduction (drug effects)

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