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Title:The role of redox oscillation in circadian physiology of the suprachiasmatic nucleus and hippocampus
Author(s):Yu, Mia
Director of Research:Gillette, Martha
Doctoral Committee Chair(s):Gillette, Martha
Doctoral Committee Member(s):Sweedler, Jonathan; Raetzman, Lori; Christian, Catherine
Department / Program:Molecular & Integrative Physl
Discipline:Molecular & Integrative Physi
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Circadian, Redox
Abstract:The suprachiasmatic nucleus (SCN) of the hypothalamus is the master regulator of the circadian clock in mammals. It generates daily rhythms of behavior, metabolism, and other important physiological processes. Misalignment of this internal circadian clock with the external environment can lead to disruption of function and disease states, such as sleep disorders, metabolic syndromes, and cardiovascular disease. The main driver of circadian behavior is a transcription-translation feedback loop of core circadian genes. Emerging evidence suggest that metabolic oscillators also play a crucial role in circadian rhythm generation. The discovery of a near-24 h oscillation of redox state in the suprachiasmatic nucleus (SCN) has put metabolism in the center of circadian biology (Wang et al., 2012), yet little is known about what drives the redox rhythm or the extent of its influence in the SCN. We hypothesize that redox oscillation is a novel circadian oscillator that both regulates and is regulated by the known circadian arms in the SCN and may play similar roles in other brain regions. Here, we propose a set of experiments to address the questions of what impacts the redox oscillation and what roles the redox oscillation play in circadian rhythm physiology. Using intra-SCN cannulation surgery to modulate the SCN in vivo and wheel-running behavior as an output of circadian timing, we determined that directly altering the SCN redox state changes the entraining effect of light on circadian behavioral rhythms of mice. We evaluated SCN redox state in the presence of tetrodotoxin (TTX) to block Na+-dependent action potentials and found that redox oscillation may be dependent upon daily rhythms of SCN neuronal activity. To evaluate whether redox state modulates neuronal circadian rhythms in other brain regions, we used real-time imaging techniques. We observed a circadian redox oscillation in the hippocampus that is anti-phase to that of the SCN. And similar to the SCN, the rhythm in redox state appears to modulate membrane excitability in hippocampal CA1 neurons. Our results demonstrate that 1) the SCN redox oscillation is a modulator of circadian physiology at the level of phase-shifting response to light, 2) the circadian redox oscillation shows interdependency with the molecular clock as well as neuronal activity rhythms, and 3) rhythms in redox state and subsequent modulation of neuronal excitability are not characteristics of only the SCN but extends to another brain region, the hippocampus. Overall, this study indicates the redox rhythm is a novel circadian oscillation that both modulates and is modulated by the known oscillators in the SCN and may play similar roles in the hippocampus.
Issue Date:2018-12-04
Rights Information:Copyright 2018 Mia Yu
Date Available in IDEALS:2019-02-07
Date Deposited:2018-12

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