Melatonin attenuates scopolamine-induced cognitive impairment via protecting against demyelination through BDNF-TrkB signaling in the mouse dentate gyrus. (1st April 2018)

• Record Type: Journal Article
• Authors: Chen, Bai Hui; Park, Joon Ha; Lee, Tae-Kyeong; Song, Minah; Kim, Hyunjung; Lee, Jae Chul; Kim, Young-Myeong; Lee, Choong-Hyun; Hwang, In Koo; Kang, Il Jun; Yan, Bing Chun; Won, Moo-Ho; Ahn, Ji Hyeon
• Is Part Of: Chemico-biological interactions. Volume 285(2018)
• Page Start: 8
• Page End: 13
• Publication Date: 2018-04-01
• Subjects: Immunohistochemistry -- Morris water maze test -- Myelinated nerve fibers -- Neurotrophic factor -- Passive avoidance test -- Western blotting; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2018.02.023
• Languages: English
• ISSNs: 0009-2797

Abstract

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. Graphical abstract: Highlights: Long-term treatment of scopolamine (Sco) induces cognitive deficits. Long-term treatment of melatonin improves Sco-induced cognitive deficits. Sco significantly decreases MBP, BDNF, and TrkB in the dentate gyrus. Melatonin restores scopolamine-induced decreases in MBP, BDNF, and TrkB.