Chronic intermittent hypoxia induces oxidative stress and inflammation in brain regions associated with early-stage neurodegeneration

Brina Snyder, Brent Shell, J. Thomas Cunningham, Rebecca L. Cunningham

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Sleep apnea is a common comorbidity of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Previous studies have shown an association between elevated oxidative stress and inflammation with severe sleep apnea. Elevated oxidative stress and inflammation are also hallmarks of neurodegenerative diseases. We show increased oxidative stress and inflammation in a manner consistent with early stages of neurodegenerative disease in an animal model of mild sleep apnea. Male rats were exposed to 7 days chronic intermittent hypoxia (CIH) for 8 h/day during the light period. Following CIH, plasma was collected and tested for circulating oxidative stress and inflammatory markers associated with proinflammatory M1 or anti-inflammatory M2 profiles. Tissue punches from brain regions associated with different stages of neurodegenerative diseases (early stage: substantia nigra and entorhinal cortex; intermediate: hippocampus; late stage: rostral ventrolateral medulla and solitary tract nucleus) were also assayed for inflammatory markers. A subset of the samples was examined for 8-hydroxydeoxyguanosine (8-OHdG) expression, a marker of oxidative stress-induced DNA damage. Our results showed increased circulating oxidative stress and inflammation. Furthermore, brain regions associated with early-stage (but not late-stage) AD and PD expressed oxidative stress and inflammatory profiles consistent with reported observations in preclinical neurodegenerative disease populations. These results suggest mild CIH induces key features that are characteristic of early-stage neurodegenerative diseases and may be an effective model to investigate mechanisms contributing to oxidative stress and inflammation in those brain regions.

Original languageEnglish
Article numbere13258
JournalPhysiological Reports
Volume5
Issue number9
DOIs
StatePublished - May 2017

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Encephalitis
Oxidative Stress
Neurodegenerative Diseases
Inflammation
Sleep Apnea Syndromes
Parkinson Disease
Alzheimer Disease
Brain
Entorhinal Cortex
Solitary Nucleus
Hypoxia
Substantia Nigra
DNA Damage
Comorbidity
Hippocampus
Anti-Inflammatory Agents
Animal Models
Light
Population

Keywords

  • Entorhinal cortex
  • RVLM
  • hippocampus
  • solitary tract nucleus
  • substantia nigra

Cite this

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title = "Chronic intermittent hypoxia induces oxidative stress and inflammation in brain regions associated with early-stage neurodegeneration",
abstract = "Sleep apnea is a common comorbidity of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Previous studies have shown an association between elevated oxidative stress and inflammation with severe sleep apnea. Elevated oxidative stress and inflammation are also hallmarks of neurodegenerative diseases. We show increased oxidative stress and inflammation in a manner consistent with early stages of neurodegenerative disease in an animal model of mild sleep apnea. Male rats were exposed to 7 days chronic intermittent hypoxia (CIH) for 8 h/day during the light period. Following CIH, plasma was collected and tested for circulating oxidative stress and inflammatory markers associated with proinflammatory M1 or anti-inflammatory M2 profiles. Tissue punches from brain regions associated with different stages of neurodegenerative diseases (early stage: substantia nigra and entorhinal cortex; intermediate: hippocampus; late stage: rostral ventrolateral medulla and solitary tract nucleus) were also assayed for inflammatory markers. A subset of the samples was examined for 8-hydroxydeoxyguanosine (8-OHdG) expression, a marker of oxidative stress-induced DNA damage. Our results showed increased circulating oxidative stress and inflammation. Furthermore, brain regions associated with early-stage (but not late-stage) AD and PD expressed oxidative stress and inflammatory profiles consistent with reported observations in preclinical neurodegenerative disease populations. These results suggest mild CIH induces key features that are characteristic of early-stage neurodegenerative diseases and may be an effective model to investigate mechanisms contributing to oxidative stress and inflammation in those brain regions.",
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