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Sickness-induced sleep is a behavior conserved across species that promotes recovery from illness, yet the underlying mechanisms are poorly understood. Here, we show that interleukin-6-like cytokine signaling from the Drosophila gut to brain glial cells regulates sleep. Under healthy conditions, this pathway promotes wakefulness. However, elevated gut cytokine signaling in response to oxidative stress - triggered by immune and inflammatory responses in the intestine - induces sleep. The cytokines Unpaired 2 and -3 are upregulated by oxidative stress in enteroendocrine cells and activate JAK-STAT signaling in glial cells, including those of the blood-brain barrier (BBB). This activity maintains elevated sleep during oxidative-stress-induced intestinal disturbances, suggesting that the JAK-STAT pathway in glia inhibits wake-promoting signaling to facilitate sleep-dependent restoration under these conditions. We find that the enteric peptide Allatostatin A (AstA) enhances wakefulness, and during intestinal oxidative stress, gut-derived Unpaired 2/3 inhibits AstA receptor expression in BBB glia, thereby sustaining an elevated sleep state during gut inflammation or illness. Taken together, our work identifies a gut-to-glial communication pathway that couples sleep with intestinal homeostasis and disease, enhancing sleep during intestinal sickness, and contributing to our understanding of how sleep disturbances arise from gastrointestinal disturbances.
Pubmed ID: 40924804
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Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsR Code used to analyze FLIC data. Functions are provided to examine interactions with food for single well and food choice experiments when fly makes physical contact with liquid food.
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Green Fluorescent Protein (GFP)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Prospero protein
View all literature mentionsThis polyclonal secondary targets IgY (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets GFP
View all literature mentionsThis monoclonal targets Repo; Reversed polarity protein
View all literature mentionsThis monoclonal targets mCherry
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsDrosophila melanogaster with name w[*] TI{2A-GAL4}AstA-R1[2A-GAL4.R] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{y[+t7.7] w[+mC]=UAS-TrpA1(B).K}attP16 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-RedStinger}4/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=upd3-GAL4.Z}2, P{UAS-GFP.U}2/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00646}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+m*]=moody-GAL4.SPG}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=tubP-GAL80[ts]}10; TM2/TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name TI{2A-GAL4}AstC[2A-GAL4]/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; TI{2A-GAL4}AstA-R2[2A-AC.GAL4]/TM3, Sb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS05683}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{y[+t7.7] w[+mC]=GMR57C10-GAL4}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMJ21208}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+m*]=GAL4}repo/TM3, Sb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name TI{2A-GAL4}Tk[2A-GAL4] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01905}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name TI{2A-GAL4}AstA[2A-GAL4] from BDSC.
View all literature mentions