Sleep is found widely in the animal kingdom. Despite this, few conserved molecular pathways that govern sleep across phyla have been described. The mammalian brain-type fatty acid binding protein (Fabp7) is expressed in astrocytes, and its mRNA oscillates in tandem with the sleep-wake cycle. However, the role of FABP7 in regulating sleep remains poorly understood. We found that the missense mutation FABP7.T61M is associated with fragmented sleep in humans. This phenotype was recapitulated in mice and fruitflies bearing similar mutations: -deficient mice and transgenic flies that express the FABP7.T61M missense mutation in astrocytes also show fragmented sleep. These results provide novel evidence for a distinct molecular pathway linking lipid-signaling cascades within astrocytes in sleep regulation among phylogenetically disparate species.
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http://dx.doi.org/10.1126/sciadv.1602663 | DOI Listing |
Neuro Oncol
December 2023
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada.
Background: Glioblastoma (GBM) stem-like cells (GSCs) are crucial drivers of treatment resistance and tumor recurrence. While the concept of "migrating" cancer stem cells was proposed a decade ago, the roles and underlying mechanisms of the heterogeneous populations of GSCs remain poorly defined.
Methods: Cell migration using GBM cell lines and patient-derived GSCs was examined using Transwell inserts and the scratch assay.
Front Syst Neurosci
June 2023
Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, United States.
Sleep and circadian rhythms are observed broadly throughout animal phyla and influence neural plasticity and cognitive function. However, the few phylogenetically conserved cellular and molecular pathways that are implicated in these processes are largely focused on neuronal cells. Research on these topics has traditionally segregated sleep homeostatic behavior from circadian rest-activity rhythms.
View Article and Find Full Text PDFNeuroglia
June 2022
Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA.
Humans with post-traumatic stress disorder (PTSD) exhibit sleep disturbances that include insomnia, nightmares, and enhanced daytime sleepiness. Sleep disturbances are considered a hallmark feature of PTSD; however, little is known about the cellular and molecular mechanisms regulating trauma-induced sleep disorders. Using a rodent model of PTSD called "Single Prolonged Stress" (SPS) we examined the requirement of the brain-type fatty acid binding protein Fabp7, an astrocyte expressed lipid-signaling molecule, in mediating trauma-induced sleep disturbances.
View Article and Find Full Text PDFFront Neurosci
June 2022
Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, United States.
Fatty acid binding proteins (FABPs) are a family of intracellular lipid chaperone proteins known to play critical roles in the regulation of fatty acid uptake and transport as well as gene expression. Brain-type fatty acid binding protein (FABP7) is enriched in astrocytes and has been implicated in sleep/wake regulation and neurodegenerative diseases; however, the precise mechanisms underlying the role of FABP7 in these biological processes remain unclear. FABP7 binds to both arachidonic acid (AA) and docosahexaenoic acid (DHA), resulting in discrete physiological responses.
View Article and Find Full Text PDFInt J Mol Sci
December 2021
Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
The heart primarily uses fatty acids as energy substrates. Adipose lipolysis is a major source of fatty acids, particularly under stress conditions. In this study, we showed that mice with selective inactivation of the lipolytic coactivator comparative gene identification-58 (CGI-58) in adipose tissue (FAT-KO mice), relative to their littermate controls, had lower circulating FA levels in the fed and fasted states due to impaired adipose lipolysis.
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