Abnormalities in the Polysomnographic, Adenosine and Metabolic Response to Sleep Deprivation in an Animal Model of Hyperammonemia

Show full item record



Permalink

http://hdl.handle.net/10138/224489

Citation

Marini , S , Santangeli , O , Saarelainen , P , Middleton , B , Chowdhury , N , Skene , D J , Costa , R , Porkka-Heiskanen , T & Montagnese , S 2017 , ' Abnormalities in the Polysomnographic, Adenosine and Metabolic Response to Sleep Deprivation in an Animal Model of Hyperammonemia ' , Frontiers in Physiology , vol. 8 , 636 . https://doi.org/10.3389/fphys.2017.00636

Title: Abnormalities in the Polysomnographic, Adenosine and Metabolic Response to Sleep Deprivation in an Animal Model of Hyperammonemia
Author: Marini, Selena; Santangeli, Olena; Saarelainen, Pirjo; Middleton, Benita; Chowdhury, Namrata; Skene, Debra J.; Costa, Rodolfo; Porkka-Heiskanen, Tarja; Montagnese, Sara
Contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
Date: 2017-08-31
Language: eng
Number of pages: 13
Belongs to series: Frontiers in Physiology
ISSN: 1664-042X
URI: http://hdl.handle.net/10138/224489
Abstract: Patients with liver cirrhosis can develop hyperammonemia and hepatic encephalopathy (HE), accompanied by pronounced daytime sleepiness. Previous studies with healthy volunteers show that experimental increase in blood ammonium levels increases sleepiness and slows the waking electroencephalogram. As ammonium increases adenosine levels invitro, and adenosine is a known regulator of sleep/wake homeostasis, we hypothesized that the sleepiness-inducing effect of ammonium is mediated by adenosine. Eight adult male Wistar rats were fed with an ammonium-enriched diet for 4 weeks; eight rats on standard diet served as controls. Each animal was implanted with electroencephalography/electromyography (EEG/EMG) electrodes and a microdialysis probe. Sleep EEG recording and cerebral microdialysis were carried out at baseline and after 6 h of sleep deprivation. Adenosine and metabolite levels were measured by high-performance liquid chromatography (HPLC) and targeted LC/MS metabolomics, respectively. Baseline adenosine and metabolite levels (12 of 16 amino acids, taurine, t4-hydroxy-proline, and acetylcarnitine) were lower in hyperammonemic animals, while putrescine was higher. After sleep deprivation, hyperammonemic animals exhibited a larger increase in adenosine levels, and a number of metabolites showed a different time-course in the two groups. In both groups the recovery period was characterized by a significant decrease in wakefulness/increase in NREM and REM sleep. However, while control animals exhibited a gradual compensatory effect, hyperammonemic animals showed a significantly shorter recovery phase. In conclusion, the adenosine/metabolite/EEG response to sleep deprivation was modulated by hyperammonemia, suggesting that ammonia affects homeostatic sleep regulation and its metabolic correlates.
Subject: hyperammonemia
hepatic encephalopathy
sleep homeostasis
adenosine
metabolomics/metabolic profiling
HEPATIC-ENCEPHALOPATHY
BASAL FOREBRAIN
PROLONGED WAKEFULNESS
LIVER-DISEASES
AMINO-ACIDS
RATS
CIRRHOSIS
AMMONIA
HOMEOSTASIS
MICRODIALYSIS
3111 Biomedicine
1184 Genetics, developmental biology, physiology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
fphys_08_00636.pdf 2.649Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record