Effects of Glucocorticoids upon Pro-inflammatory Responses to Acute Sleep Fragmentation in Mice
Grade Level at Time of Presentation
Sophomore
Major
Biology (Gatton)
Institution
Western Kentucky University
KY House District #
KY-20
KY Senate District #
KY-32
Faculty Advisor/ Mentor
Noah Ashley, PhD.
Department
Biology Dept.
Abstract
Sleep is essential to human life as it regulates cognitive, metabolic, and immunological processes. Fragmented sleep is commonly observed in humans who suffer from obstructive sleep apnea (OSA). This dysregulation of sleep can induce inflammatory responses, which causes increased levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). These responses can lead to chronic inflammation which can negatively affect human health. Using mouse models, we have previously reported that sleep fragmentation (SF) causes an increase in the expression of these pro-inflammatory genes in peripheral and brain tissue. During sleep fragmentation, glucocorticoids are released and are considered anti-inflammatory and immunosuppressive at high doses but on an acute level may stimulate immune function. We hypothesized that glucocorticoids are involved in regulating these inflammatory responses during acute SF. To investigate this, C57BL/6J male and female mice were subjected to adrenalectomy (ADX), ADX + Corticosterone, sham-ADX, or sham-ADX + Corticosterone, followed by a week to recover. Mice were then subjected to acute (24 h) SF which was simulated using cages in which bar sweeps occurred every 2 minutes continuously for 24 hours. After SF, peripheral (liver, spleen, heart, adipose, trunk blood) and brain (prefrontal cortex, hippocampus, hypothalamus) tissues were collected from the mice. RNA was extracted from tissues and corticosterone ELISAs were used to assess circulating corticosterone concentration. RT-PCR was then used to assess pro-inflammatory cytokine gene expression in peripheral and brain tissues. The results obtained from this study will aid in identifying potential pathways mediating inflammatory responses that could lead to better therapeutic treatments for OSA and other sleep disorders.
Effects of Glucocorticoids upon Pro-inflammatory Responses to Acute Sleep Fragmentation in Mice
Sleep is essential to human life as it regulates cognitive, metabolic, and immunological processes. Fragmented sleep is commonly observed in humans who suffer from obstructive sleep apnea (OSA). This dysregulation of sleep can induce inflammatory responses, which causes increased levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). These responses can lead to chronic inflammation which can negatively affect human health. Using mouse models, we have previously reported that sleep fragmentation (SF) causes an increase in the expression of these pro-inflammatory genes in peripheral and brain tissue. During sleep fragmentation, glucocorticoids are released and are considered anti-inflammatory and immunosuppressive at high doses but on an acute level may stimulate immune function. We hypothesized that glucocorticoids are involved in regulating these inflammatory responses during acute SF. To investigate this, C57BL/6J male and female mice were subjected to adrenalectomy (ADX), ADX + Corticosterone, sham-ADX, or sham-ADX + Corticosterone, followed by a week to recover. Mice were then subjected to acute (24 h) SF which was simulated using cages in which bar sweeps occurred every 2 minutes continuously for 24 hours. After SF, peripheral (liver, spleen, heart, adipose, trunk blood) and brain (prefrontal cortex, hippocampus, hypothalamus) tissues were collected from the mice. RNA was extracted from tissues and corticosterone ELISAs were used to assess circulating corticosterone concentration. RT-PCR was then used to assess pro-inflammatory cytokine gene expression in peripheral and brain tissues. The results obtained from this study will aid in identifying potential pathways mediating inflammatory responses that could lead to better therapeutic treatments for OSA and other sleep disorders.