Peripheral-to-Central Neuroimmune Communication and the Sun: Implications for Addiction and Neurodegenerative Disease Pathology

Abstract

The format of this thesis is as follows: a general introduction, a literature review, a research proposal, a systematic review, a general discussion, references and appendices. Both the literature review and systematic review (Chapters 2 and 4) have been published in peer-reviewed journals and are presented in their original manuscript format, except that language had been adjusted into Australian English for consistency, and literature citations have been collated within the reference section. The work presented herein explores how peripheral ultraviolet light applied to the skin can affect the central nervous system and behaviour, with a focus on the clinical translation to prevalent neurological disorders. First, the impact of solar irradiation on the integumentary system and evidence of skin-brain-communication pathways are introduced. This discussion builds the concept that peripheral UV signals arising in the skin may result in global manifestations via the brain (Chapter 1). The idea of skin-brain communication is further explored with a literature review linking sunbathing, UV exposure seeking and addictive behaviour (Chapter 2). In this chapter, a novel hypothesis is presented suggesting that UV-induced inflammatory signalling may influence neuronal circuits to increase the addictive-like behaviours observed in frequent tanners (Chapter 2). This idea provides the basis for a research proposal (Chapter 3) detailing planned experimental work to investigate whether UV radiation influences mesolimbic dopaminergic systems within the brain, and if inflammation plays a substantial role. Chapter 3 is presented as a research proposal as the work could not be completed due to unforeseen circumstances, which significantly reduced my capacity to continue with the study. Appendices have been included to exhibit the pilot research that had commenced. The final research chapter (Chapter 4) focuses on the role of sun-induced or administered vitamin D and its influence on neurological health. This chapter presents a systematic review of published literature that investigates whether the presumed protective benefits from vitamin D, in neurodegenerative disease, is dependent on route of administration.