Melatonin improves vascular cognitive impairment induced by ischemic stroke by remyelination via activation of ERK1/2 signaling and restoration of glutamatergic synapses in the gerbil hippocampus.
Vascular dementia affects cognition by damaging axons and myelin. Melatonin is pharmacologically associated with various neurological disorders. In this study, effects of melatonin on cognitive impairment and related mechanisms were investigated in an animal model of ischemic vascular dementia (IVD). Melatonin was intraperitoneally administered to adult gerbils after transient global cerebral ischemia (tGCI) for 25 days beginning 5 days after tGCI. Cognitive impairment was examined using a passive avoidance test and the Barnes maze test. To investigate mechanisms of restorative effects by melatonin, neuronal damage/death, myelin basic protein (MBP, a marker for myelin), Rip (a marker for oligodendrocyte), extracellular signal-regulated protein kinase1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2), and vesicular glutamate transporter (VGLUT)-1 (a glutamatergic synaptic marker) in the hippocampal Cornu Ammonis 1 area (CA1) were evaluated using immunohistochemistry. Melatonin treatment significantly improved tGCI-induced cognitive impairment. Death of CA1 pyramidal neurons after tGCI was not affected by melatonin treatment. However, melatonin treatment significantly increased MBP immunoreactivity and numbers of Rip-immunoreactive oligodendrocytes in the ischemic CA1. In addition, melatonin treatment significantly increased ERK1/2 and p-ERK1/2 immunoreactivities in oligodendrocytes in the ischemic CA1. Furthermore, melatonin treatment significantly increased VGLUT-1 immunoreactive structures in the ischemic CA1. These results indicate that long-term melatonin treatment after tGCI improves cognitive deficit via restoration of myelin, increase of oligodendrocytes which is closely related to the activation of ERK1/2 signaling, and increase of glutamatergic synapses in the ischemic brain area.
['Chen|Bai Hui|BH|', 'Park|Joon Ha|JH|', 'Lee|Yun Lyul|YL|', 'Kang|Il Jun|IJ|', 'Kim|Dae Won|DW|', 'Hwang|In Koo|IK|', 'Lee|Choong-Hyun|CH|', 'Yan|Bing Chun|BC|', 'Kim|Young-Myeong|YM|', 'Lee|Tae-Kyeong|TK|', 'Lee|Jae Chul|JC|', 'Won|Moo-Ho|MH|', 'Ahn|Ji Hyeon|JH|']
D000818:Animals D019208:Brain-Derived Neurotrophic Factor D056547:CA1 Region, Hippocampal D016923:Cell Death D060825:Cognitive Dysfunction D005849:Gerbillinae D018698:Glutamic Acid D006624:Hippocampus D002546:Ischemic Attack, Transient D020935:MAP Kinase Signaling System D008297:Male D008550:Melatonin D023421:Models, Animal D009186:Myelin Sheath D009474:Neurons D009836:Oligodendroglia D000074586:Remyelination D020521:Stroke D013569:Synapses
Melatonin ERK1/2 Glutamatergic synapse Vascular dementia Myelin Oligodendrocyte