Effects of Sleep Deprivation (SD) on Rats via ERK1/2 Signaling Pathway

Abstract

Background Sleep deprivation (SD) is common in humans, and sleep loss has a significant influence on health and produces related diseases. Orexin-A has been demonstrated to play a role in physiological processes, including feeding, sleep/wake cycle, and energy metabolism. The aim of this study was to investigate the effect of SD on rats and to define the underlying mechanism. Material/Methods We constructed an SD rat model. The Morris water maze test was used to assess rat learning and memory. Imaging of hippocampus and hippocampal tissue in rats were captured by magnetic resonance imaging or electron microscopy. We used the CCK-8 kit to assess cell viability. The level of protein was measured using Western blot analysis, and qRT-PCR was used to evaluate mRNA level. Results SD rats had poorer learning and memory and had damage to the hippocampus. SD resulted in shrinkage of hippocampal volume and encephalocele size. SD increased the expression of Orexin-A, OX1R, OX2R, and PARP-1, and decreased the expression of ERK1/2 and p-ERK1/2. Orexin-A (0–10 μM) improved neuron viability, whereas orexin-A (10–100 μM) attenuated neuron viability. SB334867 treatment reduced the viability of neurons treated with orexin-A. NU1025 treatment increased cell viability, especially in neurons treated with orexin-A. SB334867 treatment decreased the p-ERK1/2 levels in neurons treated with orexin-A. NU1025 increased the expression of p-ERK1/2 in neurons treated with orexin-A. Conclusions SD decreases learning and memory through damage to the hippocampus. Higher concentrations of orexin-A had a major negative effect on hippocampal neurons via OX1R and PARP-1 through inhibition of the ERK1/2 signaling pathway.

Amide Proton Transfer-Weighted Imaging Detects Hippocampal Proteostasis Disturbance Induced by Sleep Deprivation at 7.0 T MRI

“…In this study, a significant difference in the hippocampal APTw signal was observed in sleep-deprived rats than that in normal rats, but no significant difference was observed in the hippocampal volume. This finding indicates that the APTw signal can reflect alterations in the hippocampus more sensitively than the hippocampal volume, which was reported to reduce after 5 weeks of sleep deprivation . Notably, a hyperintensity was observed in the cerebral ventricle, which may be due to the artifacts generated by the cerebrospinal fluid flow.…”

“…This finding indicates that the APTw signal can reflect alterations in the hippocampus more sensitively than the hippocampal volume, which was reported to reduce after 5 weeks of sleep deprivation. 30 Notably, a hyperintensity was observed in the cerebral ventricle, which may be due to the artifacts generated by the cerebrospinal fluid flow. This sign reminds us that we should avoid including the cerebral ventricle when analyzing the APTw signal in the hippocampus.…”

G-protein coupled receptors and synaptic plasticity in sleep deprivation

“…Sleep deprivation affects the ability to concentrate, intake information and mediate that information through neuronal signalling, learn as well as process memories for consolidation. Furthermore, it is affected by the signalling and expression profiles of many biological molecules including the GPCRs[ 20 , 21 ]. These functions are related to the different stages of sleep and hence there are stage specific implications of sleep deprivation.…”

Sleep, brain vascular health and ageing

“…In addition, proteins like Sirt1, PGC1, FOXO, p66shc, and poly (ADP-ribose) polymerase 1 (PARP1) (Eros et al 2017) are shown to participate in early vascular ageing (Harvey et al 2015). Scientific evidences strongly indicate that SD adversely affects the above-mentioned signalling molecules (Chang et al 2009;Sugiyama et al 1995;Vecsey et al 2012;Wang et al 2019). This spurt us to propose and interlink the impact of SD on brain vascular ageing.…”

“…However, high levels of PARP-1 cause cell death. Increased protein levels of orexin-A, OX1R, OX2R and PARP-1 and decreased protein level of ERK1/2 are observed in the hippocampus of SD rats (Wang et al 2019). PARP1-1, the sensor of DNA damage, is a new melatonin-dependent regulator of senescence-associated secretory phenotype (SASP) gene induction on oncogene-induced senescence (OIS).…”