Medical Research

Washington State University

James Krueger, Cheryl Dykstra-Aiello, Ilia Karatsoreos, Alexander Panchenko
Spokane, WA
December 2019

In all humans, host cells and microbes live in a delicate symbiotic balance.  The gut microbiome affects cognition, emotion, sleep, circadian rhythms, and additional brain functions.  Yet, the causal brain mechanisms behind these effects are unknown.  A small literature, including past work by Washington State University (WSU) investigators, indicates that bacterial cell wall peptidoglycan (PG) is present in normal brain and changes with sleep loss.  These findings provide an intriguing new understanding of what it means to be human – bacteria participate in human neurobiology.  The WSU investigators posit that PGs regulate physiological brain functions including sleep and circadian rhythms.  They further expect that non-pathological alterations of sleep or circadian rhythms, e.g. acute sleep deprivation or simulated jetlag, induce dynamic changes in brain PG levels which, in turn, could induce changes in the expression of genes associated with sleep/wake cycles and circadian rhythms.  Using mouse models, the WSU investigators have demonstrated that the mRNA of a PG-binding peptide in the brain increases after acute sleep deprivation.  This peptide induces the expression of sleep regulatory cytokines involved in circadian rhythms.  In this project, the WSU team plans to measure the levels of PG and of the PG-binding peptide in the mouse brain under normal circadian rhythms and sleep-wake cycles.  They would determine how disrupting sleep or circadian rhythms drives changes in the levels of PG and PG-binding peptide along with other proteins related to circadian rhythms.  Lastly, using in vitro neuronal/glial co-cultures that simulate sleeplike states, the investigators would characterize the molecular mechanisms linking PG levels to cytokines and sleep.  Successful completion of this project would advance our understanding of the relationship among the microbiome, immune responses, sleep, and circadian rhythms.

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