title: Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus.
abstract: Loss of sleep may result in memory impairment. However, little is known about the biochemical basis for memory deficits induced by sleep deprivation. Extracellular signal-regulated kinase (ERK) is involved in memory consolidation in different tasks. Phosphorylation of ERK is necessary for its activation and is an important step in mediating neuronal responses to synaptic activities. The aim of the present study was to determine the effects of total sleep deprivation (TSD) on memory and ERK phosphorylation in the brain. Rats were trained in Morris water maze to find a hidden platform (a spatial task) or a visible platform (a nonspatial task) after 6 h TSD or spontaneous sleep. TSD had no effect on spatial learning, but significantly impaired spatial memory tested 24 h after training. Nonspatial learning and memory were not impaired by TSD. Phospho-ERK levels in the hippocampus were significantly reduced after 6 h TSD compared to the controls and returned to the control levels after 2 h recovery sleep. Total ERK1 and ERK2 were slightly increased after 6 h TSD and returned to the control levels after 2 h recovery sleep. These alterations were not observed in the cortex after TSD. Protein phosphotase-1 and mitogen-activated protein kinase phosphatase-2, which dephosphorylates phospho-ERK, were also measured, but they were not altered by TSD. The impairments of both spatial memory and ERK phosphorylation indicate that the hippocampus is vulnerable to sleep loss. These results are consistent with the idea that decreased ERK activation in the hippocampus is involved in sleep deprivation-induced spatial memory impairment.
authors.affiliation: Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey 17033, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Guan
authors.forename: Xuwen
authors.initials: X
authors.lastname: Peng
authors.forename: Jidong
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D054637:Dual-Specificity Phosphatases; D006624:Hippocampus / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D054639:Mitogen-Activated Protein Kinase Phosphatases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D054637:Dual-Specificity Phosphatases; C094132:Dusp4 protein, rat; D017027:Protein Tyrosine Phosphatases