Author ORCID Identifier

0000-0002-4852-8993

Date of Graduation

8-2022

Document Type

Thesis (MS)

Program Affiliation

Neuroscience

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Dr. Kristin Eckel-Mahan, Ph.D.

Committee Member

Dr. Zheng Chen, Ph.D.

Committee Member

Dr. Seung-Hee Yoo, Ph.D.

Committee Member

Dr. Nicholas Justice, Ph.D.

Committee Member

Dr. Joya Chandra, Ph.D.

Committee Member

Dr. J. Leigh Leasure, Ph.D.

Abstract

Maintaining our internal circadian (i.e. 24 -hour) clock is imperative to our daily biological and mental well-being. Large epidemiological studies have shown that disruptions of our circadian rhythms can lead to poor mental health, metabolic diseases, and various types of cancer. Various external cues that have become a part of the modern times such as electricity, shift -work, rapid travel across various time zones, easier access to nutritionally unbalanced food items, and various rigid social demands have deleterious effects on our internal clock, and generally reduce robustness of the circadian clock. The two following projects aim to examine two fundamental aspects of the circadian clock mechanism in health and disease: 1) exercise as an entrainment mechanism for the clock; and 2) targeting of clock proteins to reduce proliferation and survival in acute myeloid leukemia. Both projects center on the important role of the circadian clock protein brain and muscle ARNT-like factor (BMAL1), which is a transcription factor critical for maintaining cellular rhythmicity. Loss of the protein in the PVN of the hypothalamus can lead to arrhythmicity, but can be rescued by exercise. In the case of acute myeloid leukemia, this protein can be targeted to slow the proliferation of transformed cells. vii Together, these data suggest that the exploitation of circadian mechanisms of entrainment and molecular targeting can be used to rescue the damage inflicted by circadian disruption.

Keywords

circadian rhythms, exercise, entrainment, nobiletin

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