Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB expression by improving sleep architecture at high altitude

Abstract

AimsSleep loss at high altitude (HA) play major role in worsening of neuropsychological functions, such as attention, memory and decision making. This study investigates the role of phosphorylated delta sleep inducing peptide (p-DSIP) in improving sleep architecture during chronic hypobaric hypoxia (HH) exposure and restoration of spatial navigational memory. MethodsMorris water maze (MWM) trained rats were exposed to HH at 7620 m. p-DSIP was injected intra-peritoneally (10 μg/Kg bw) during HH exposure as an intervention against sleep alteration. Sleep architecture was recorded telemetrically before and during HH exposure. Monoamines were estimated by high performance liquid chromatography from brain stem (BS) and hypothalamus. CREB and p-CREB level in hippocampus was studied by western blotting and expression of different monoamine regulatory enzymes in BS was measured by flow cytometry. Naloxone (1 mg/kg bw), a μ opioid receptor antagonist of sleep inducing effect of DSIP was also studied. Key findingsp-DSIP injection daily in circadian active period (18.30 h) during chronic HH enhanced non rapid eye movement sleep, rapid eye movement sleep as well as improved MWM performance of rats. p-DSIP treatment showed lower monoamine level and tyrosine hydroxylase (TH) expression and increased monoamine oxidase A (MAO A), glutamic acid decarboxylase (GAD) and Choline acetyltransferase (ChAT) expression. Further, naloxone altered navigational memory by decreasing the CREB and p-CREB level in hippocampus suggesting suppression of sleep inducing effect of p-DSIP. SignificanceOur study demonstrates that improvement of sleep quality by p-DSIP restores spatial memory by up regulating CREB phosphorylation during simulated high altitude hypoxia.