NOX2 inhibition enables retention of the circadian clock in BV2 microglia and primary macrophages

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 6, 2023

Sustained neuroinflammation is a major contributor to the progression of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD) diseases. Neuroinflammation, like other cellular processes, affected by circadian clock. Microglia, resident immune cells in brain, act contributors are under influence Microglial responses activation, recruitment, cytokine expression rhythmic their response various stimuli. While link between rhythms clear, significant gaps remain our understanding this complex relationship. To gain greater relationship, interaction microglial clock enzyme NADPH Oxidase Isoform 2 (NOX2) was studied; NOX2 essential for production reactive oxygen species (ROS) oxidative stress, an integral characteristic neuroinflammation.

Language: Английский

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Nutrients and the Circadian Clock: A Partnership Controlling Adipose Tissue Function and Health

Nutrients, Journal Year: 2022, Volume and Issue: 14(10), P. 2084 - 2084

Published: May 16, 2022

White adipose tissue (WAT) is a metabolic organ with flexibility to retract and expand based on energy storage utilization needs, processes that are driven via the coordination of different cells within tissue. WAT comprised mature adipocytes (MA) stromal vascular cell fraction (SVF), which include progenitor (APCs), endothelial (AEC) infiltrating immune cells. APCs have ability proliferate undergo adipogenesis form MA, main constituents being predominantly composed white, triglyceride-storing unilocular lipid droplets. While adiposity health controlled by diet aging, endogenous circadian (24-h) biological clock body highly active in tissue, from adipocyte adipocytes, may play unique role function. To some extent, 24-h rhythms rely rhythmic intake, but individual proteins also thought be important for healthy fat. Here we discuss how why might so this depot, temporal qualitative aspects intake roles maintaining fat throughout aging.

Language: Английский

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One‐Step Assembly of Versatile Multifunctional Coatings Based on Host‐Guest and Polyphenol Chemistry

Small, Journal Year: 2023, Volume and Issue: 19(22)

Published: Feb. 8, 2023

Developing a facile, efficient, and versatile polyphenol coating strategy exploring its novel applications are of great significance in the fields material surfaces interfaces. Herein, one-step assembly for constructing tannic acid (TA) coatings via solvent evaporation method is reported using TA polycyclodextrin (PCD) particles (TPP). TPP with high phenolic group activity 88% integrates advantages host-guest chemistry. The former can drive dynamically assemble into large collective aggregation activated by temperature or density, latter provides excellent adhesion properties to substrates (0.9 mg cm-2 ). (TPC) rapidly on various within 1 h at 37 °C while availability feed (≈90%). resulting TPC not only high-temperature steam-sensitive use as an anti-fake mask but also pH-sensitive transforming free-standing film under physiological conditions. Moreover, metal ions functional incorporate extend including antibacterial activity, enhanced stability, conductivity. This work expands builds up efficient preparation platform multiapplication prospects fields.

Language: Английский

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Macrophages and the Extracellular Matrix

Results and problems in cell differentiation, Journal Year: 2024, Volume and Issue: unknown, P. 55 - 87

Published: Jan. 1, 2024

Language: Английский

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Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: March 23, 2023

Alzheimer's disease (AD) is a progressive neurodegenerative that results in cognitive impairment and often accompanied by anxiety. In this study, we investigated whether the activation of VTAVgat neurons could reduce anxiety APP/PS1 mice. We hypothesized acute social defeat stress (SDS) would lead to mice, alleviate anxiety.We exposed mice SDS assessed using open field test elevated plus-arm test. Activated was tested cfos staining. Sleep quality detected electroencephalogram after or non-SDS procedure. duration, sleep latency, non-rapid eye movement (NREM) percentage were analyzed. chemogenetically activated deschloroclozapine.Our showed led as evidenced increased anxiety-related behaviors tests. Activation an increase primarily due decrease latency NREMs. However, poor. Chemogenetical improved relieved SDS-induced Furthermore, state correlated negatively with duration NREM positively theta power density mice.Our study provides evidence alleviates suggesting poor may exacerbate AD. These findings have important implications for treatment AD, targeting be potential therapeutic approach.

Language: Английский

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Single-cell variations of circadian clock and immune gene expression in microglia and neurodegeneration

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 16, 2024

Summary We investigated the diurnal rhythmicity of gene expression in microglia, resident macrophages brain, health and disease. Using RNA sequencing single-cell analysis by RNAscope, we examined wild-type mice R6/2 transgenic mouse model Huntington’s disease (HD). Our findings suggest context-dependent rhythmic exhibiting substantial variability between individual cells brain regions over 24 hours. Notably, observed loss key clock genes microglia from symptomatic but not presymptomatic mice. Moreover, identified de novo 24-hour altered patterns immune-related associated with neurodegenerative diseases circadian reprogramming context neurodegeneration.

Language: Английский

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MYC disrupts transcriptional and metabolic circadian oscillations in cancer and promotes enhanced biosynthesis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 3, 2023

The molecular circadian clock, which controls rhythmic 24-hour oscillation of genes, proteins, and metabolites in healthy tissues, is disrupted across many human cancers. Deregulated expression the MYC oncoprotein has been shown to alter clock leading a disruption cancer types. It remains unclear what benefit cells gain from suppressing oscillation, how this loss impacts global gene metabolism cancer. We hypothesized that or its paralog N-MYC (collectively termed herein) suppress upregulate pathways involved biosynthesis static, non-oscillatory fashion. To test this, distinct types with inducible were examined, using time-series RNA-sequencing metabolomics, determine extent activation disrupts pathways, metabolites. focused our analyses on changed common multiple cell line models. report here over 85% oscillating while instead promoting enhanced ribosomal mitochondrial biogenesis suppressed attachment pathways. Notably, when activated, biosynthetic programs formerly flipped being upregulated an oscillation-free manner. Further, ablates nutrient transporter proteins greatly upregulating expression, surface localization, intracellular amino acid pools. Finally, we metabolite oscillations temporal segregation nucleotide metabolism. Our results demonstrate releases metabolic processes control, may provide advantage cells.

Language: Английский

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The PAICE suite reveals circadian posttranscriptional timing of noncoding RNAs and spliceosome components in Mus musculus macrophages

G3 Genes Genomes Genetics, Journal Year: 2022, Volume and Issue: 12(9)

Published: July 25, 2022

Circadian rhythms broadly regulate physiological functions by tuning oscillations in the levels of mRNAs and proteins to 24-h day/night cycle. Globally assessing which are timed clock necessitates accurate recognition RNA protein data, particularly large omics data sets. Tools that employ fixed-amplitude models have previously been used positive effect. However, amplitude change circadian required a new generation analytical software enhance identification these oscillations. To address this gap, we created Pipeline for Amplitude Integration Exploration suite. Here, demonstrate suite's increased utility detect trends through joint modeling Mus musculus macrophage transcriptome proteome. Our enhanced detection confirmed extensive posttranscriptional regulation macrophages but highlighted some reported discrepancy between mRNA was due noise data. We further applied suite investigate timing noncoding RNAs, documenting long RNAs small nuclear control spliceosome complex. By tracking oscillating complex using PAICE suite, noted regulates spliceosome, major As most above-noted had damped changes their oscillations, work highlights importance thorough enumeration omics-scale datasets.

Language: Английский

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Prognostic utility of rhythmic components in 24-hour ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 5, 2023

Chronic kidney disease (CKD) represents a significant global burden. Hypertension is modifiable risk factor for rapid progression of CKD.

Language: Английский

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Glial control of sphingolipid levels sculpts diurnal remodeling of circadian circuits

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: March 19, 2022

Summary Structural plasticity in the brain often necessitates dramatic remodeling of neuronal processes and attendant reorganization cytoskeleton membranes. While cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural remains unclear. We show that specific glial cells Drosophila produce Glucocerebrosidase (GBA) to locally catabolize sphingolipids. Sphingolipid accumulation drives lysosomal dysfunction, causing gba1b mutants harbor protein aggregates cycle across circadian time are regulated by neural activity, clock, sleep. vast majority membrane stable day, a subset, highly enriched sphingolipids, cycles daily -dependant fashion. In parallel, clock neurons remodel their neurites, growing shrinking day shape behavior. Remarkably, this relies on temporally offset sphingolipid biosynthesis catabolism. Thus, dynamic regulation glia enables diurnal circuit proper

Language: Английский

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