A conserved role for <i>frizzled</i> in sleep architecture

Gessner, Nicholas R; Peiravi, Morteza; Zhang, Fan; Yimam, Shemsiya; Springer, Danielle; Harbison, Susan T

doi:10.1093/sleepadvances/zpad045

Cited by 2 publications

(2 citation statements)

References 79 publications

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“…and nighttime (mobile) activity and immobility (50). Vagotomized mice exhibited decreased fatigue, as measured by mobility (distance traveled) and immobility (sleep/inactivity), specifically during nighttime cycles (Fig.…”

Section: Vagotomy Benefits Neurological Function In Hcc Tumor-bearing...mentioning

confidence: 94%

“…Following facility acclimatization, vagotomized HCC mice underwent a battery of established behavioral tests, including phenotyping, open field test (OFT), and Y-maze (Fig. 4A) (48,50,51). To address neurological behaviors elicited by vagotomy versus tumor, a "Baseline" series of tests were performed prior to RIL175 tumor implantation.…”

Section: Vagotomy Benefits Neurological Function In Hcc Tumor-bearing...mentioning

confidence: 99%

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The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Bauer,

Trehan,

Ruf

et al. 2024

Preprint

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Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8+ T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

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Section: Vagotomy Benefits Neurological Function In Hcc Tumor-bearing...mentioning

confidence: 94%

Section: Vagotomy Benefits Neurological Function In Hcc Tumor-bearing...mentioning

confidence: 99%

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Bauer,

Trehan,

Ruf

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Evo-devo applied to sleep research: an approach whose time has come

Brown

2024

Sleep Advances

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Sleep occurs in all animals but its amount, form, and timing varies considerably between species and between individuals. Currently, little is known about the basis for these differences, in part because we lack a complete understanding of the brain circuitry controlling sleep-wake states and markers for the cell-types which can identify similar circuits across phylogeny. Here, I explain the utility of an ‘Evo-devo’ approach for comparative studies of sleep regulation and function as well as for sleep medicine. This approach focuses on the regulation of evolutionary ancient transcription factors which act as master controllers of cell-type specification. Studying these developmental transcription factor cascades can identify novel cell clusters which control sleep and wakefulness, reveal the mechanisms which control differences in sleep timing, amount and expression and identify the timepoint in evolution when different sleep-wake control neurons appeared. Spatial transcriptomic studies which identify cell clusters based on transcription factor expression will greatly aid this approach. Conserved developmental pathways regulate sleep in mice, Drosophila and C. Elegans. Members of the LIM Homeobox (Lhx) gene family control the specification of sleep and circadian neurons in the forebrain and hypothalamus. Increased Lhx9 activity may account for increased orexin/hypocretin neurons and reduced sleep in Mexican cavefish. Other transcription factor families specify sleep-wake circuits in the brainstem, hypothalamus, and basal forebrain. Expression of transcription factors allows generation of specific cell-types for transplantation approaches. Furthermore, mutations in developmental transcription factors are linked to variation in sleep duration in humans, risk for restless legs syndrome and sleep-disordered breathing. This paper is part of the Genetic and other molecular underpinnings of sleep, sleep disorders, and circadian rhythms including translational approaches collection.

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A conserved role for frizzled in sleep architecture

Cited by 2 publications

References 79 publications

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Evo-devo applied to sleep research: an approach whose time has come

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