scholarly journals Simulating Sleep Apnea by Exposure to Intermittent Hypoxia Induces Inflammation in the Lung and Liver

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Darlan Pase da Rosa ◽  
Luiz Felipe Forgiarini ◽  
Diego Baronio ◽  
Cristiano Andrade Feijó ◽  
Dênis Martinez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Caspase 3 ◽  
Hypoxia Inducible Factor ◽  
Central Sleep Apnea ◽  
Upper Airway ◽  
Vascular Endothelial ◽  
Endogenous Antioxidant ◽  
Endothelial Growth Factor

Sleep apnea is a breathing disorder that results from momentary and cyclic collapse of the upper airway, leading to intermittent hypoxia (IH). IH can lead to the formation of free radicals that increase oxidative stress, and this mechanism may explain the association between central sleep apnea and nonalcoholic steatohepatitis. We assessed the level of inflammation in the lung and liver tissue from animals subjected to intermittent hypoxia and simulated sleep apnea. A total of 12 C57BL/6 mice were divided into two groups and then exposed to IH (n=6) or a simulated IH (SIH) (n=6) for 35 days. We observed an increase in oxidative damage and other changes to endogenous antioxidant enzymes in mice exposed to IH. Specifically, the expression of multiple transcription factors, including hypoxia inducible factor (HIF-1α), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF-α), inducible NO synthase (iNOS), vascular endothelial growth factor (VEGF), and cleaved caspase 3 were shown to be increased in the IH group. Overall, we found that exposure to intermittent hypoxia for 35 days by simulating sleep apnea leads to oxidative stress, inflammation, and increased activity of caspase 3 in the liver and lung.

scholarly journals A role for Hypoxia Inducible Factor 1a (HIF1a) in intermittent hypoxia-dependent changes to spatial memory and synaptic plasticity

2019 ◽  
Author(s):  
Alejandra Arias-Cavieres ◽  
Maggie A. Khuu ◽  
Chinwendu U Nwakudu ◽  
Jasmine E. Barnard ◽  
Gokhan Dalgin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sleep Apnea ◽  
Learning And Memory ◽  
Intermittent Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Long Term Potentiation ◽  
Barnes Maze ◽  
Glutamatergic Transmission ◽  
Term Potentiation

AbstractIntermittent hypoxia (IH), a key feature of sleep apnea, increases the oxygen regulated transcription factor Hypoxia Inducible Factor 1a (HIF1a). Although recognized for its role in IH-dependent changes in cardio-respiratory physiology, it remains unclear how IH-dependent HIF1a signaling affects neurophysiology underlying learning and memory. This study examines how IH affects hippocampal associated learning and memory in wildtype mice and mice heterozygous for the HIF1a gene (HIF1a+/-). In wild-type mice, ten days of IH impaired performance in the Barnes maze increased hippocampal HIF1a and elevated protein carbonyls. These behavioral and biochemical effects of IH were accompanied by a decrease in the N-Methyl-D-Aspartate receptor (NMDAr) and an attenuation of long-term potentiation (LTP) in area CA1. In HIF1a+/-, IH did not impair Barnes maze performance, increase hippocampal HIF1a, or enhance protein carbonyl content. At the network level, IH neither led to a decrease in NMDAr nor impaired LTP. Concurrent antioxidant treatment during IH mitigated the IH-dependent effects on the Barnes maze performance and LTP in wildtype mice. Our findings indicate that IH-dependent HIF1a signaling leads to oxidative stress and reduces NMDAr to impair LTP in area CA1, which contributes to IH-dependent deficits in learning and memory associated with the hippocampus.SignificanceIntermittent Hypoxia is a hallmark of sleep apnea and decreases the threshold for cognitive deficit. We demonstrate that intermittent hypoxia-dependent HIF1a signaling contributes to impairments in hippocampal associated memory. This is co-incidental with HIF1a-mediated alternations in synaptic physiology and increased oxidative stress.Key pointsIntermittent hypoxia (IH) is a hallmark of sleep apnea and is known to cause learning and memory deficits.Hypoxia Inducible Factor 1a (HIF1a), is associated with IH-dependent changes in physiology.IH exposure causes increased hippocampal HIF1a in wild type mice and is associated with elevated oxidative stress, impairments to spatial memory, and suppression of long term potentiation (LTP).IH-dependent suppression of LTP is co-incidental with diminished NMDA receptor contribution to glutamatergic transmission.Following IH, mice heterozygous for HIF1a (HIF1a+/-) do not show an increase in HIF1a and oxidative stress, or changes in either behavior or glutamatergic transmission.

scholarly journals Intermittent hypoxia has organ-specific effects on oxidative stress

2008 ◽  
Vol 295 (4) ◽  
pp. R1274-R1281 ◽  
Author(s):  
Jonathan Jun ◽  
Vladimir Savransky ◽  
Ashika Nanayakkara ◽  
Shannon Bevans ◽  
Jianguo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Nadph Oxidase ◽  
Intermittent Hypoxia ◽  
Upper Airway ◽  
Oxidase Inhibitor ◽  
Enzyme Activation ◽  
Systemic Oxidative Stress ◽  
Obstructive Sleep

Obstructive sleep apnea is characterized by upper airway collapse, leading to intermittent hypoxia (IH). It has been postulated that IH-induced oxidative stress may contribute to several chronic diseases associated with obstructive sleep apnea. We hypothesize that IH induces systemic oxidative stress by upregulating NADPH oxidase, a superoxide-generating enzyme. NADPH oxidase is regulated by a cytosolic p47phox subunit, which becomes phosphorylated during enzyme activation. Male C57BL/6J mice were exposed to IH with an inspired O2 fraction nadir of 5% 60 times/h during the 12-h light phase (9 AM–9 PM) for 1 or 4 wk. In the aorta and heart, IH did not affect lipid peroxidation [malondialdehyde (MDA) level], nitrotyrosine level, or p47phox expression and phosphorylation. In contrast, in the liver, exposure to IH for 1 wk resulted in a trend to an increase in MDA levels, whereas IH for 4 wk resulted in a 38% increase in MDA levels accompanied by upregulation of p47phox expression and phosphorylation. Administration of an NADPH oxidase inhibitor, apocynin, during IH exposure attenuated IH-induced increases in hepatic MDA. In p47phox-deficient mice, MDA levels were higher at baseline and, unexpectedly, decreased during IH. In conclusion, oxidative stress levels and pathways under IH conditions are organ and duration specific.

Sleep and Violence*

1984 ◽  
Vol 29 (2) ◽  
pp. 132-134 ◽  
Author(s):  
L.B. Raschka
Keyword(s):  
Differential Diagnosis ◽  
Sleep Apnea ◽  
Central Sleep Apnea ◽  
Upper Airway ◽  
Violent Behaviour ◽  
Car Accidents ◽  
Prevention And Treatment ◽  
Respiratory Pathology ◽  
The Brain

Most violence connected with sleep disorder is assumed to be related to sleep walking. It is less well known that other sleep disorders can also give rise to violence. The role of narcolepsy in car accidents is mentioned. Sleep drunkenness can lead to confusion resulting in violent behaviour especially on forced awakening. This condition is associated to sleep apnea. Primary or central sleep apnea is caused by disorders of the brain stem affecting the respiratory center. Secondary or upper airway sleep apnea can be caused by virtually any condition that results in cessation of the airflow due to occlusion of the upper airway. The author describes one patient who engaged in assaultive behaviour on forced awakening following earlier alcohol consumption. The pathomechanism of violent behaviour generated by a combination of sleep apnea and respiratory pathology is described. The differential diagnosis, prevention and treatment is outlined. The use of polysomnography in diagnosis and the potentially dangerous effects of drugs with respiratory depressing effects is highlighted.

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