Abstract
The astrocyte brain-type fatty acid binding protein (Fabp7) gene expression cycles globally throughout mammalian brain, and is known to regulate sleep in multiple species, including humans. The mechanisms that control circadian Fabp7 gene expression are not completely understood and may include core circadian clock components. Here we examined the circadian expression of Fabp7 mRNA in the hypothalamus of core clock gene Bmal1 knock-out (KO) mice. We observed that the circadian rhythm of Fabp7 mRNA expression is blunted, while overall Fabp7 mRNA levels are significantly higher in Bmal1 KO compared to control (C57BL/6 J) mice. We did not observe any significant changes in levels of hypothalamic mRNA expression of Fabp3 or Fabp5, two other fatty acid binding proteins expressed in mammalian brain, between Bmal1 KO and control mice. These results suggest that Fabp7 gene expression is regulated by circadian processes and may represent a molecular link controlling the circadian timing of sleep with sleep behavior.
Highlights
Sleep behavior is exhibited by virtually every species studied, while the precise function of sleep remains unknown
Fatty-acid binding proteins (Fabp) comprise a family of small (~ 15 kDa) hydrophobic ligand binding carriers with high affinity for long-chain fatty-acids for intracellular transport, and are associated with metabolic, inflammatory, and energy homeostasis pathways [8, 9]. These include three that are expressed in the adult mammalian central nervous system (CNS), and are Fabp3 (H-Fabp), Fabp5 (E-Fabp), and Fabp7 (B-Fabp)
Fabp3 is predominantly expressed in neurons, Fabp5 is expressed in multiple cell types, including both neurons and glia, and Fabp7 is enriched in astrocytes and neural progenitors
Summary
Sleep behavior is exhibited by virtually every species studied, while the precise function of sleep remains unknown. Circadian rhythms are regulated by a well-defined and phylogenetically conserved transcriptional/translational autoregulatory negative feedback loop [3], which includes the core clock gene Bmal1 [4]. Bmal1 is a basic helix-loop-helix transcription factor known to heterodimerize with core circadian factors CLOCK or NPAS2 and bind to E-box elements in the promoter of downstream target genes to
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