Brain Lipid Homeostasis as a Primary Function of Sleep: Insights from Drosophila melanogaster

Sleep is a conserved behavioral state necessary for most animal life. In this dissertation, I focus on the intriguing relationship between sleep and healthy brain function. Phylogenetically, sleep is observed in animals with neurons; developmentally, in the fruit fly, Drosophila melanogaster, sleep behavior is first detected during the same larval stage as neuron-glia interactions that support neurogenesis. Glial are central to brain integration of neuronal activity, external and peripheral cues, and metabolic changes, which all influence organismal behaviors like sleep. Here, I present the basis for glial support of neuronal health through lipid homeostasis as a primary function of sleep using adult Drosophila melanogaster as a model. In Chapter 1, I highlight the links between lipid metabolism and sleep by presenting previous studies in glia and in invertebrate model systems. I discuss the rationale for focusing on glial lipids across development in wildtype animals and in neurodegenerative, pathological contexts. In Chapter 2, my co-authors and I propose a neuron-glia lipid metabolic cycle through the study of neuronal and glial mitochondrial health and lipid transfer during sleep and wake. Glia accumulate neuronal mitochondrial damage and lipids in a pattern that correlates with sleep need. In Chapter 3, I further investigate the relationship between glial lipid accumulation and sleep to determine whether lipid storage or some other lipid processing step, lipid class, or species is sleep-promoting. Through brain imaging, sleep studies, and lipidomic profiling of sorted neurons and glia by sex, I discover a neutral lipid class, monoacylglycerols, that regulates sleep through glial modulation despite sex-specific differences in brain lipid composition. My dissertation concludes with Chapter 4, where my findings are discussed and additional investigations of brain lipid homeostasis are proposed that may reveal why or how sleep is necessary for animal life.

Author dc:creator

• Pyfrom, Elana, Simone

Advisor dc:contributor.advisor

• Sehgal, Amita

• Neuroscience and Neurobiology
• Biochemistry, Biophysics, and Structural Biology
• Biology

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/62708

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/62708