Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.

<h4>Background</h4>Physiological circadian rhythms (CRs) are complex processes with 24-hour oscillations that regulate diverse biological functions. Chronic weekly light/dark (LD) shifting (CR disruption; CRD) in mice results in colonic hyperpermeability. However, the mechanisms behind t...

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Autores principales:	Laura Tran, Sarah B Jochum, Maliha Shaikh, Sherry Wilber, Lijuan Zhang, Dana M Hayden, Christopher B Forsyth, Robin M Voigt, Faraz Bishehsari, Ali Keshavarzian, Garth R Swanson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/36b3a464284d4261bc98ad06ea77960a
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spelling	oai:doaj.org-article:36b3a464284d4261bc98ad06ea77960a2021-12-02T20:03:56ZCircadian misalignment by environmental light/dark shifting causes circadian disruption in colon.1932-620310.1371/journal.pone.0251604https://doaj.org/article/36b3a464284d4261bc98ad06ea77960a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251604https://doaj.org/toc/1932-6203<h4>Background</h4>Physiological circadian rhythms (CRs) are complex processes with 24-hour oscillations that regulate diverse biological functions. Chronic weekly light/dark (LD) shifting (CR disruption; CRD) in mice results in colonic hyperpermeability. However, the mechanisms behind this phenomenon are incompletely understood. One potential innovative in vitro method to study colonic CRs are colon organoids. The goals of this study were to utilize circadian clock gene Per2 luciferase reporter (Per2::Luc) mice to measure the effects of chronic LD shifting on colonic tissue circadian rhythmicity ex vivo and to determine if organoids made from shifted mice colons recapitulate the in vivo phenotype.<h4>Methods</h4>Non-shifted (NS) and shifted (S) BL6 Per2::Luc mice were compared after a 22-week experiment. NS mice had a standard 12h light/12h dark LD cycle throughout. S mice alternated 12h LD patterns weekly, with light from 6am-6pm one week followed by shifting light to 6pm-6am the next week for 22 weeks. Mice were tested for intestinal permeability while colon tissue and organoids were examined for CRs of bioluminescence and proteins of barrier function and cell fate.<h4>Results</h4>There was no absolute difference in NS vs. S 24h circadian period or phase. However, chronic LD shifting caused Per2::Luc S mice colon tissue to exhibit significantly greater variability in both the period and phase of Per2::Luc rhythms than NS mice colon tissue and organoids. Chronic LD shifting also resulted in increased colonic permeability of the Per2::Luc mice as well as decreased protein markers of intestinal permeability in colonic tissue and organoids from shifted Per2:Luc mice.<h4>Conclusions</h4>Our studies support a model in which chronic central circadian disruption by LD shifting alters the circadian phenotype of the colon tissue and results in colon leakiness and loss of colonic barrier function. These CRD-related changes are stably expressed in colon stem cell derived organoids from CRD mice.Laura TranSarah B JochumMaliha ShaikhSherry WilberLijuan ZhangDana M HaydenChristopher B ForsythRobin M VoigtFaraz BishehsariAli KeshavarzianGarth R SwansonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0251604 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laura Tran Sarah B Jochum Maliha Shaikh Sherry Wilber Lijuan Zhang Dana M Hayden Christopher B Forsyth Robin M Voigt Faraz Bishehsari Ali Keshavarzian Garth R Swanson Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.
description	<h4>Background</h4>Physiological circadian rhythms (CRs) are complex processes with 24-hour oscillations that regulate diverse biological functions. Chronic weekly light/dark (LD) shifting (CR disruption; CRD) in mice results in colonic hyperpermeability. However, the mechanisms behind this phenomenon are incompletely understood. One potential innovative in vitro method to study colonic CRs are colon organoids. The goals of this study were to utilize circadian clock gene Per2 luciferase reporter (Per2::Luc) mice to measure the effects of chronic LD shifting on colonic tissue circadian rhythmicity ex vivo and to determine if organoids made from shifted mice colons recapitulate the in vivo phenotype.<h4>Methods</h4>Non-shifted (NS) and shifted (S) BL6 Per2::Luc mice were compared after a 22-week experiment. NS mice had a standard 12h light/12h dark LD cycle throughout. S mice alternated 12h LD patterns weekly, with light from 6am-6pm one week followed by shifting light to 6pm-6am the next week for 22 weeks. Mice were tested for intestinal permeability while colon tissue and organoids were examined for CRs of bioluminescence and proteins of barrier function and cell fate.<h4>Results</h4>There was no absolute difference in NS vs. S 24h circadian period or phase. However, chronic LD shifting caused Per2::Luc S mice colon tissue to exhibit significantly greater variability in both the period and phase of Per2::Luc rhythms than NS mice colon tissue and organoids. Chronic LD shifting also resulted in increased colonic permeability of the Per2::Luc mice as well as decreased protein markers of intestinal permeability in colonic tissue and organoids from shifted Per2:Luc mice.<h4>Conclusions</h4>Our studies support a model in which chronic central circadian disruption by LD shifting alters the circadian phenotype of the colon tissue and results in colon leakiness and loss of colonic barrier function. These CRD-related changes are stably expressed in colon stem cell derived organoids from CRD mice.
format	article
author	Laura Tran Sarah B Jochum Maliha Shaikh Sherry Wilber Lijuan Zhang Dana M Hayden Christopher B Forsyth Robin M Voigt Faraz Bishehsari Ali Keshavarzian Garth R Swanson
author_facet	Laura Tran Sarah B Jochum Maliha Shaikh Sherry Wilber Lijuan Zhang Dana M Hayden Christopher B Forsyth Robin M Voigt Faraz Bishehsari Ali Keshavarzian Garth R Swanson
author_sort	Laura Tran
title	Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.
title_short	Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.
title_full	Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.
title_fullStr	Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.
title_full_unstemmed	Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.
title_sort	circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/36b3a464284d4261bc98ad06ea77960a
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Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon.

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