Author ORCID Identifier

https://orcid.org/0000-0002-0387-9263

Semester

Summer

Date of Graduation

2023

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Not Listed

Committee Chair

Courtney A. DeVries, Ph.D.

Committee Member

Randy J. Nelson, Ph.D.

Committee Member

Zachary M. Weil, Ph.D.

Committee Member

Gordon P. Meares, Ph.D.

Committee Member

Vincent S. Setola, Ph.D.

Abstract

Artificial Light at Night Disrupts Pain Behavior and Cerebrovascular Structure in Mice

Jacob R. Bumgarner

Circadian rhythms are intrinsic biological processes that fluctuate in function with a period of approximately 24 hours. These rhythms are precisely synchronized to the 24- hour day of the Earth by external rhythmic signaling cues. Solar light-dark cycles are the most potent environmental signaling cue for terrestrial organisms to align internal rhythms with the external day. Proper alignment and synchrony of internal circadian rhythms with external environmental rhythms are essential for health and optimal biological function.

The modern human environment on Earth is no longer conducive to properly aligned circadian rhythms. Following the industrial revolution, artificial lighting and an ever-growing 24-hour global economy have shifted humans away from natural environments suited for rhythmic behavior and physiology. Humans, and much of the natural environment, are routinely exposed to circadian rhythm disruptors. The most pervasive disruptor of circadian rhythms is artificial light at night (ALAN).

A growing 80% of humans on Earth are exposed to ALAN beyond natural nighttime environmental lighting levels. ALAN exposure is associated with numerous negative consequences on behavior and physiology, including neuroinflammation, cardiovascular disease, and altered immune function. This dissertation examines two previously uninvestigated effects of ALAN exposure on physiology and behavior in mice.

In Part 1, I investigated the effects of ALAN exposure on pain behavior in mice. I observed that ALAN exposure had detrimental effects on rodent pain behavior in contexts of both health and models of human disease. ALAN exposure heightened responsiveness to noxious cold stimuli and innocuous mechanical touch. Differences in these effects were noted based on sex and disease state. I conclude this section with a report on the mechanisms by which ALAN exposure altered pain behavior.

In Part 2, I investigated the effects of ALAN exposure on cerebrovascular structure in mice. To conduct these investigations, I first developed VesselVio, an open-source application for the analysis and visualization of vasculature datasets. Using this application and additional analytical frameworks, I examined the effects of short-term ALAN exposure on hippocampal vasculature in mice. ALAN exposure reduced hippocampal vascular density in mice, with notable regional sex differences. I also observed that ALAN exposure altered hippocampal vascular network connectivity and structure, with persistent regional sex differences.

The data in this dissertation contribute to the ever-growing field of circadian rhythm biology focused on studying circadian rhythm disruption. These data highlight the continuing need to mitigate the pervasiveness of ALAN in human and natural environments. Most importantly, the results presented in this dissertation emphasize the need to consider ALAN as a mitigating factor for the treatment of both cardiovascular disease and pain.

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