Modafinil treatment prevents REM sleep deprivation-induced brain function impairment by increasing MMP-9 expression.
Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats.
Department of Neurology, Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China
Bin
B
He
Hua
H
Peng
Ying
Y
Zhao
Hui
H
Zhou
Zhongxin
Z
Zhao
D000704:Analysis of Variance; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism*; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology* / Q000517:prevention & control; D000077408:Modafinil; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012892:Sleep Deprivation / Q000150:complications* / Q000503:physiopathology; D012895:Sleep, REM; D016704:Synapsins / Q000187:drug effects / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D016704:Synapsins; D020780:Matrix Metalloproteinase 9; D000077408:Modafinil