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Melatonin Improves Cognitive Deficits via Restoration of Cholinergic Dysfunction in a Mouse Model of Scopolamine-Induced Amnesia.

Abstract
Melatonin is known to improve cognitive deficits, and its functions have been studied in various disease models, including Alzheimer's disease. In this study, we investigated effects of melatonin on cognition and the cholinergic system of the septum and hippocampus in a mouse model of scopolamine-induced amnesia. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally to mice for 2 and 4 weeks. The Morris water maze and passive avoidance tests revealed that both treatments of scopolamine significantly impaired spatial learning and memory; however, 2- and 4-week melatonin treatments significantly improved spatial learning and memory. In addition, scopolamine treatments significantly decreased protein levels and immunoreactivities of choline acetyltransferase (ChAT), high-affinity choline transporter (CHT), vesicular acetylcholine transporter (VAChT), and muscarinic acetylcholine receptor M1 (M1R) in the septum and hippocampus. However, the treatments with melatonin resulted in increased ChAT-, CHT-, VAChT-, and M1R-immunoreactivities and their protein levels in the septum and hippocampus. Our results demonstrate that melatonin treatment is effective in improving the cognitive deficits via restoration of the cholinergic system in the septum and hippocampus of a mouse model of scopolamine-induced amnesia.
AuthorsBai Hui Chen, Joon Ha Park, Dae Won Kim, Jinseu Park, Soo Young Choi, In Hye Kim, Jeong Hwi Cho, Tae-Kyeong Lee, Jae Chul Lee, Choong-Hyun Lee, In Koo Hwang, Young-Myeong Kim, Bing Chun Yan, Il Jun Kang, Bich Na Shin, Yun Lyul Lee, Myoung Cheol Shin, Jun Hwi Cho, Young Joo Lee, Yong Hwan Jeon, Moo-Ho Won, Ji Hyeon Ahn
JournalACS chemical neuroscience (ACS Chem Neurosci) Vol. 9 Issue 8 Pg. 2016-2024 (08 15 2018) ISSN: 1948-7193 [Electronic] United States
PMID28901737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Membrane Transport Proteins
  • Nootropic Agents
  • Vesicular Acetylcholine Transport Proteins
  • choline transporter
  • Scopolamine
  • Choline O-Acetyltransferase
  • Melatonin
Topics
  • Amnesia (drug therapy, metabolism)
  • Animals
  • Choline O-Acetyltransferase (metabolism)
  • Cognition (drug effects, physiology)
  • Cognitive Dysfunction (drug therapy, metabolism)
  • Disease Models, Animal
  • Male
  • Maze Learning (drug effects)
  • Melatonin (pharmacology)
  • Membrane Transport Proteins (metabolism)
  • Mice, Inbred ICR
  • Nootropic Agents (pharmacology)
  • Scopolamine
  • Spatial Memory (drug effects)
  • Vesicular Acetylcholine Transport Proteins (metabolism)

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