Microglia Are Necessary to Regulate Sleep after an Immune Challenge

Microglia play a critical role in the neuroimmune response, but little is known about the role of microglia in sleep following an inflammatory trigger. Nevertheless, decades of research have been predicated on the assumption that an inflammatory trigger increases sleep through microglial activation....

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Main Authors: Rachel K. Rowe, Tabitha R. F. Green, Katherine R. Giordano, J. Bryce Ortiz, Sean M. Murphy, Mark R. Opp
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/11/8/1241
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author Rachel K. Rowe
Tabitha R. F. Green
Katherine R. Giordano
J. Bryce Ortiz
Sean M. Murphy
Mark R. Opp
author_facet Rachel K. Rowe
Tabitha R. F. Green
Katherine R. Giordano
J. Bryce Ortiz
Sean M. Murphy
Mark R. Opp
author_sort Rachel K. Rowe
collection DOAJ
description Microglia play a critical role in the neuroimmune response, but little is known about the role of microglia in sleep following an inflammatory trigger. Nevertheless, decades of research have been predicated on the assumption that an inflammatory trigger increases sleep through microglial activation. We hypothesized that mice (<i>n</i> = 30) with depleted microglia using PLX5622 (PLX) would sleep less following the administration of lipopolysaccharide (LPS) to induce inflammation. Brains were collected and microglial morphology was assessed using quantitative skeletal analyses and physiological parameters were recorded using non-invasive piezoelectric cages. Mice fed PLX diet had a transient increase in sleep that dissipated by week 2. Subsequently, following a first LPS injection (0.4 mg/kg), mice with depleted microglia slept more than mice on the control diet. All mice were returned to normal rodent chow to repopulate microglia in the PLX group (10 days). Nominal differences in sleep existed during the microglia repopulation period. However, following a second LPS injection, mice with repopulated microglia slept similarly to control mice during the dark period but with longer bouts during the light period. Comparing sleep after the first LPS injection to sleep after the second LPS injection, controls exhibited temporal changes in sleep patterns but no change in cumulative minutes slept, whereas cumulative sleep in mice with repopulated microglia decreased during the dark period across all days. Repopulated microglia had a reactive morphology. We conclude that microglia are necessary to regulate sleep after an immune challenge.
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spelling doaj.art-f3ec24e27bd94f018a804927b7587dad2023-12-01T23:26:41ZengMDPI AGBiology2079-77372022-08-01118124110.3390/biology11081241Microglia Are Necessary to Regulate Sleep after an Immune ChallengeRachel K. Rowe0Tabitha R. F. Green1Katherine R. Giordano2J. Bryce Ortiz3Sean M. Murphy4Mark R. Opp5Department of Integrative Physiology, University of Colorado, Boulder, CO 80301, USADepartment of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USADepartment of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USADepartment of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USADepartment of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USADepartment of Integrative Physiology, University of Colorado, Boulder, CO 80301, USAMicroglia play a critical role in the neuroimmune response, but little is known about the role of microglia in sleep following an inflammatory trigger. Nevertheless, decades of research have been predicated on the assumption that an inflammatory trigger increases sleep through microglial activation. We hypothesized that mice (<i>n</i> = 30) with depleted microglia using PLX5622 (PLX) would sleep less following the administration of lipopolysaccharide (LPS) to induce inflammation. Brains were collected and microglial morphology was assessed using quantitative skeletal analyses and physiological parameters were recorded using non-invasive piezoelectric cages. Mice fed PLX diet had a transient increase in sleep that dissipated by week 2. Subsequently, following a first LPS injection (0.4 mg/kg), mice with depleted microglia slept more than mice on the control diet. All mice were returned to normal rodent chow to repopulate microglia in the PLX group (10 days). Nominal differences in sleep existed during the microglia repopulation period. However, following a second LPS injection, mice with repopulated microglia slept similarly to control mice during the dark period but with longer bouts during the light period. Comparing sleep after the first LPS injection to sleep after the second LPS injection, controls exhibited temporal changes in sleep patterns but no change in cumulative minutes slept, whereas cumulative sleep in mice with repopulated microglia decreased during the dark period across all days. Repopulated microglia had a reactive morphology. We conclude that microglia are necessary to regulate sleep after an immune challenge.https://www.mdpi.com/2079-7737/11/8/1241gliainflammationsleep–wake disturbancesmicroglia depletionplx5622
spellingShingle Rachel K. Rowe
Tabitha R. F. Green
Katherine R. Giordano
J. Bryce Ortiz
Sean M. Murphy
Mark R. Opp
Microglia Are Necessary to Regulate Sleep after an Immune Challenge
Biology
glia
inflammation
sleep–wake disturbances
microglia depletion
plx5622
title Microglia Are Necessary to Regulate Sleep after an Immune Challenge
title_full Microglia Are Necessary to Regulate Sleep after an Immune Challenge
title_fullStr Microglia Are Necessary to Regulate Sleep after an Immune Challenge
title_full_unstemmed Microglia Are Necessary to Regulate Sleep after an Immune Challenge
title_short Microglia Are Necessary to Regulate Sleep after an Immune Challenge
title_sort microglia are necessary to regulate sleep after an immune challenge
topic glia
inflammation
sleep–wake disturbances
microglia depletion
plx5622
url https://www.mdpi.com/2079-7737/11/8/1241
work_keys_str_mv AT rachelkrowe microgliaarenecessarytoregulatesleepafteranimmunechallenge
AT tabitharfgreen microgliaarenecessarytoregulatesleepafteranimmunechallenge
AT katherinergiordano microgliaarenecessarytoregulatesleepafteranimmunechallenge
AT jbryceortiz microgliaarenecessarytoregulatesleepafteranimmunechallenge
AT seanmmurphy microgliaarenecessarytoregulatesleepafteranimmunechallenge
AT markropp microgliaarenecessarytoregulatesleepafteranimmunechallenge