Abstract Title

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

RAD Assignment Number

109

Presenter Name

Brina Snyder

Abstract

Age is the highest risk factor for the development of neurodegenerative diseases (ND), such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). As life expectancy increases, the incidence of ND is projected to rise accordingly. Increased ND incidence will be associated with high healthcare costs. Currently, no cure exists for ND and diagnosis occurs at advanced stages, which foreshadows a financial healthcare crisis. Therefore, early identification of patients at risk for ND may provide opportunities for more effective therapies. Since ND is associated with increased oxidative stress (OS) and inflammation, these markers could be used to identify patients at risk for ND. Multiple environmental factors can be an oxidative stressor, and thus exacerbate inflammation induced ND risk. One such environmental factor that increases OS is sleep apnea (SA), a common ND comorbidity. However, it is unknown if SA induced oxidative stress activates neuroinflammation in areas associated with ND.

To model SA in rats, chronic intermittent hypoxia was used. Male rats were exposed to six minute chronic intermittent hypoxia (CIH) cycles, during which oxygen levels were rapidly decreased from 21% to 10% then returned to normal room air levels, eight hours a day during the light phase for seven days. Plasma and tissue from hippocampus (HIPP), entorhinal cortex (ETC), substantia nigra (SN), rostral ventrolateral medulla (RVLM), and solitary tract nucleus (NTS) were collected and tested for levels of OS and inflammation, using Advanced Oxidative Protein Products (AOPP) and multiplex immunoassays, respectively.

OS markers and inflammation were elevated in the plasma of rats exposed to CIH compared to control rats. Differences in neuroinflammatory markers within tissues were observed. Specifically, inflammatory markers in the RVLM were significantly decreased in animals exposed to CIH while TNF-a and IL-6 were elevated in the SN. TNF-a was positively associated with plasma OS and the cytokine associated with inflammatory cell recruitment, KC-Gro, exhibited the same pattern in the ETC. The ETC and SN are areas associated with initial neurodegenerative processes in AD and PD, respectively.

CIH may contribute to processes involved in early ND pathology by elevating OS and inflammation in critical brain regions. These results indicate that SA can exacerbate ND by increasing OS-induced neuroinflammation. Therefore, treatment of SA could be one consideration in preventing ND.

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

Age is the highest risk factor for the development of neurodegenerative diseases (ND), such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). As life expectancy increases, the incidence of ND is projected to rise accordingly. Increased ND incidence will be associated with high healthcare costs. Currently, no cure exists for ND and diagnosis occurs at advanced stages, which foreshadows a financial healthcare crisis. Therefore, early identification of patients at risk for ND may provide opportunities for more effective therapies. Since ND is associated with increased oxidative stress (OS) and inflammation, these markers could be used to identify patients at risk for ND. Multiple environmental factors can be an oxidative stressor, and thus exacerbate inflammation induced ND risk. One such environmental factor that increases OS is sleep apnea (SA), a common ND comorbidity. However, it is unknown if SA induced oxidative stress activates neuroinflammation in areas associated with ND.

To model SA in rats, chronic intermittent hypoxia was used. Male rats were exposed to six minute chronic intermittent hypoxia (CIH) cycles, during which oxygen levels were rapidly decreased from 21% to 10% then returned to normal room air levels, eight hours a day during the light phase for seven days. Plasma and tissue from hippocampus (HIPP), entorhinal cortex (ETC), substantia nigra (SN), rostral ventrolateral medulla (RVLM), and solitary tract nucleus (NTS) were collected and tested for levels of OS and inflammation, using Advanced Oxidative Protein Products (AOPP) and multiplex immunoassays, respectively.

OS markers and inflammation were elevated in the plasma of rats exposed to CIH compared to control rats. Differences in neuroinflammatory markers within tissues were observed. Specifically, inflammatory markers in the RVLM were significantly decreased in animals exposed to CIH while TNF-a and IL-6 were elevated in the SN. TNF-a was positively associated with plasma OS and the cytokine associated with inflammatory cell recruitment, KC-Gro, exhibited the same pattern in the ETC. The ETC and SN are areas associated with initial neurodegenerative processes in AD and PD, respectively.

CIH may contribute to processes involved in early ND pathology by elevating OS and inflammation in critical brain regions. These results indicate that SA can exacerbate ND by increasing OS-induced neuroinflammation. Therefore, treatment of SA could be one consideration in preventing ND.