Ontogenesis of the molecular response to sleep loss

Muheim, Christine; Ford, Kaitlyn; Medina, E; Singletary, Kristan G.; Peixoto, Lucı́a; Frank, Marcos G.

doi:10.1016/j.nbscr.2023.100092

Cited by 6 publications

(8 citation statements)

References 76 publications

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“…Using bulk RNA-seq we detect 8,505 differentially expressed genes after SD, while simultaneously recovering 83% of known positive control genes (Figure 5). Although this is not the first study to use bulk RNA-seq to understand the effect of SD on the bulk cortical transcriptome, we detect between 2000-7000 more differentially expressed genes driven by sleep/wake than previously published studies in the cortex and hippocampus 5,6,9,21 . This increase in sensitivity is largely due to differences in methodology on RNA-seq data analysis, such as additional normalization to removal unwanted variance (e.g.…”

Section: Discussioncontrasting

confidence: 82%

“…RUV-seq) and simultaneous transcript and gene level analysis using nonparametric testing and inferential uncertainty (Fishpond/Swish) 19 . Incorporating inferential uncertainty alone increases the number of DEGs considerably in our own data compared to our recently published study 9 , while also allowing for differential transcript expression and usage analysis after SD for the first time. We detect 15,525 differentially expressed (Figure 5) and 2,314 differentially used (corresponding 1,575 genes) transcripts (Figure 6A).…”

Section: Discussionmentioning

confidence: 87%

“…Thus, understanding the molecular consequences of SD is of fundamental importance in neuroscience. We and others have shown that in rodents SD strongly affects the brain transcriptome [4][5][6][7][8][9][10][11][12][13] . It was initially thought that there was little agreement on the effects of SD.…”

Section: Introductionmentioning

confidence: 81%

“…In this study we performed for the first time snRNA-seq and bulk RNA-seq in parallel with multiple independent biological replicates in response to sleep deprivation (SD) in the adult male mouse frontal cortex. Prior analyses have focused on bulk gene-level analysis [4][5][6][7][8][9][10][11][12][13]21 , or do not include independent biological replicates 22 . Thus to date it was not possible to define what may be occurring at the isoform level or to detect changes specific to particular cell types in response to SD.…”

Section: Discussionmentioning

confidence: 99%

“…Mice were sacrificed by live cervical dislocation (alternating between home cage controls and sleep deprived mice), decapitated, and the frontal cortex was swiftly dissected on a cold block. Tissue was flash frozen in liquid nitrogen and stored at -80°C until processing 9,32 . This protocol was repeated over a 5 day period, and all tissue was collected within the first 15 min of the hour.…”

Section: Bulk Rna-seq Gene Expression Study After Sd Tissue Collectionmentioning

confidence: 99%

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A Global Transcriptional Atlas of the Effect of Sleep Deprivation in the Mouse Frontal Cortex

Ford,

Zuin,

Righelli

et al. 2023

Preprint

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Sleep deprivation (SD) has negative effects on brain function. Sleep problems are prevalent in neurodevelopmental, neurodegenerative and psychiatric disorders. Thus, understanding the molecular consequences of SD is of fundamental importance in neuroscience. In this study, we present the first simultaneous bulk and single-nuclear (sn)RNA sequencing characterization of the effects of SD in the mouse frontal cortex. We show that SD predominantly affects glutamatergic neurons, specifically in layers 4 and 5, and produces isoform switching of thousands of transcripts. At both the global and cell-type specific level, SD has a large repressive effect on transcription, down-regulating thousands of genes and transcripts; underscoring the importance of accounting for the effects of sleep loss in transcriptome studies of brain function. As a resource we provide extensive characterizations of cell types, genes, transcripts and pathways affected by SD; as well as tutorials for data analysis.

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Section: Discussioncontrasting

confidence: 82%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Bulk Rna-seq Gene Expression Study After Sd Tissue Collectionmentioning

confidence: 99%

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A Global Transcriptional Atlas of the Effect of Sleep Deprivation in the Mouse Frontal Cortex

Ford,

Zuin,

Righelli

et al. 2023

Preprint

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Developing forebrain synapses are uniquely vulnerable to sleep loss

Gay,

Chartampila,

Lord

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Sleep is an essential behavior that supports lifelong brain health and cognition. Neuronal synapses are a major target for restorative sleep function and a locus of dysfunction in response to sleep deprivation (SD). Synapse density is highly dynamic during development, becoming stabilized with maturation to adulthood, suggesting sleep exerts distinct synaptic functions between development and adulthood. Importantly, problems with sleep are common in neurodevelopmental disorders including autism spectrum disorder (ASD). Moreover, early life sleep disruption in animal models causes long-lasting changes in adult behavior. Divergent plasticity engaged during sleep necessarily implies that developing and adult synapses will show differential vulnerability to SD. To investigate distinct sleep functions and mechanisms of vulnerability to SD across development, we systematically examined the behavioral and molecular responses to acute SD between juvenile (P21 to P28), adolescent (P42 to P49), and adult (P70 to P100) mice of both sexes. Compared to adults, juveniles lack robust adaptations to SD, precipitating cognitive deficits in the novel object recognition task. Subcellular fractionation, combined with proteome and phosphoproteome analysis revealed the developing synapse is profoundly vulnerable to SD, whereas adults exhibit comparative resilience. SD in juveniles, and not older mice, aberrantly drives induction of synapse potentiation, synaptogenesis, and expression of perineuronal nets. Our analysis further reveals the developing synapse as a putative node of convergence between vulnerability to SD and ASD genetic risk. Together, our systematic analysis supports a distinct developmental function of sleep and reveals how sleep disruption impacts key aspects of brain development, providing insights for ASD susceptibility.

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A conserved role for frizzled in sleep architecture

Gessner,

Peiravi,

Zhang

et al. 2023

Sleep Advances

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Previous studies of natural variants in Drosophila melanogaster implicated the Wnt signaling receptor frizzled in sleep. Given that the Wnt signaling pathway is highly conserved across species, we hypothesized that frizzled class receptor 1 (Fzd1), the murine homolog of frizzled, would also have a role in sleep. Using a CRISPR transgenic approach, we removed most of the Fzd1 coding region from C57BL/6N mice. We used a video assay to measure sleep characteristics in Fzd1-deficient mice. As Wnt signaling is known to affect visuospatial memory, we also examined the impact of the deletion on learning and memory using the Novel Object Recognition (NOR) paradigm. Fzd1-deficient mice had altered sleep compared to littermate controls. The mice did not respond differently to the NOR paradigm compared to controls but did display anxiety-like behavior. Our strategy demonstrates that the study of natural variation in Drosophila sleep translates into candidate genes for sleep in vertebrate species such as the mouse.

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Ontogenesis of the molecular response to sleep loss

Cited by 6 publications

References 76 publications

A Global Transcriptional Atlas of the Effect of Sleep Deprivation in the Mouse Frontal Cortex

A Global Transcriptional Atlas of the Effect of Sleep Deprivation in the Mouse Frontal Cortex

Developing forebrain synapses are uniquely vulnerable to sleep loss

A conserved role for frizzled in sleep architecture

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