Adenosine triggers early astrocyte reactivity that provokes microglial responses and drives the pathogenesis of sepsis-associated encephalopathy in mice DOI Creative Commons
Qilin Guo, Davide Gobbo, Na Zhao

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 27, 2024

Molecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during first 6 hours of peripheral lipopolysaccharide (LPS)-evoked (6 hpi), plasma level adenosine quickly increased and enhanced tone central extracellular which then provoked neuroinflammation by triggering early astrocyte reactivity. Specific ablation astrocytic Gi protein-coupled A1 receptors (A1ARs) prevented this reactivity reduced levels inflammatory factors (e.g., CCL2, CCL5, CXCL1) astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, immune cell infiltration, neuronal dysfunction, depression-like behaviour mice. Chemogenetic stimulation signaling A1AR-deficent astrocytes at 2 4 hpi LPS injection could restore behaviour, highlighting rather than microglia as drivers neuroinflammation. Our results identify towards an important pathway driving SAE highlight potential targeting A1ARs for therapeutic intervention.

Language: Английский

Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators DOI
Zhaofa Wu, Dayu Lin, Yulong Li

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(5), P. 257 - 274

Published: March 31, 2022

Language: Английский

Citations

159
A sensitive GRAB sensor for detecting extracellular ATP in vitro and in vivo DOI Creative Commons
Zhaofa Wu, Kaikai He, Yue Chen

et al.

Neuron, Journal Year: 2021, Volume and Issue: 110(5), P. 770 - 782.e5

Published: Dec. 22, 2021

Language: Английский

Citations

133
A fluorescent sensor for spatiotemporally resolved imaging of endocannabinoid dynamics in vivo DOI
Ao Dong, Kaikai He, Barna Dudok

et al.

Nature Biotechnology, Journal Year: 2021, Volume and Issue: 40(5), P. 787 - 798

Published: Nov. 11, 2021

Language: Английский

Citations

132
Adenosine, caffeine, and sleep–wake regulation: state of the science and perspectives DOI Creative Commons
Carolin Reichert, Tom Deboer, Hans‐Peter Landolt

et al.

Journal of Sleep Research, Journal Year: 2022, Volume and Issue: 31(4)

Published: May 16, 2022

Summary For hundreds of years, mankind has been influencing its sleep and waking state through the adenosinergic system. ~100 years now, systematic research performed, first started by testing effects different dosages caffeine on behaviour. About 70 ago, adenosine itself entered picture as a possible ligand receptors where hooks an antagonist to reduce sleepiness. Since scientific demonstration that this is indeed case, progress fast. Today, widely accepted endogenous sleep‐regulatory substance. In review, we discuss current science in model organisms humans working mechanisms sleep. We critically investigate evidence for direct involvement homeostatic whether differ between acute intake chronic consumption. addition, review more recent levels may also influence functioning circadian clock address question homeostasis interact signalling. final section, perspectives clinical applications accumulated knowledge over last century improve sleep‐related disorders. conclude our highlighting some open questions need be answered, better understand how exactly regulate

Language: Английский

Citations

90
A genetically encoded sensor measures temporal oxytocin release from different neuronal compartments DOI
Tongrui Qian, Huan Wang, Peng Wang

et al.

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 41(7), P. 944 - 957

Published: Jan. 2, 2023

Language: Английский

Citations

82
Lights, fiber, action! A primer on in vivo fiber photometry DOI Creative Commons
Eleanor H. Simpson, Thomas Akam, Tommaso Patriarchi

et al.

Neuron, Journal Year: 2023, Volume and Issue: 112(5), P. 718 - 739

Published: Dec. 15, 2023

Fiber photometry is a key technique for characterizing brain-behavior relationships in vivo. Initially, it was primarily used to report calcium dynamics as proxy neural activity via genetically encoded indicators. This generated new insights into brain functions including movement, memory, and motivation at the level of defined circuits cell types. Recently, opportunity discovery with fiber has exploded development an extensive range fluorescent sensors biomolecules neuromodulators peptides that were previously inaccessible critical advance, combined availability affordable "plug-and-play" recording systems, made monitoring molecules high spatiotemporal precision during behavior highly accessible. However, while opening exciting avenues research, rapid expansion applications occurred without coordination or consensus on best practices. Here, we provide comprehensive guide help end-users execute, analyze, suitably interpret studies.

Language: Английский

Citations

51
Unraveling the dynamics of dopamine release and its actions on target cells DOI Creative Commons
Tanya Sippy, Nicolas X. Tritsch

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(3), P. 228 - 239

Published: Jan. 10, 2023

Language: Английский

Citations

45
Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission DOI Creative Commons

Chenyan Ma,

Bing Li, Daniel Silverman

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(2), P. 249 - 258

Published: Jan. 18, 2024

Abstract Sleep interacts reciprocally with immune system activity, but its specific relationship microglia—the resident cells in the brain—remains poorly understood. Here, we show mice that microglia can regulate sleep through a mechanism involving G i -coupled GPCRs, intracellular Ca 2+ signaling and suppression of norepinephrine transmission. Chemogenetic activation strongly promoted sleep, whereas pharmacological blockade P2Y12 receptors decreased sleep. Two-photon imaging cortex showed P2Y12–G elevated , this elevation largely abolished -induced increase. Microglia level also increased at natural wake-to-sleep transitions, caused partly by reduced levels. Furthermore, biosensor significantly levels, increasing adenosine concentration. These findings indicate reciprocal interactions

Language: Английский

Citations

40
40 Hz light flickering promotes sleep through cortical adenosine signaling DOI Creative Commons
Xuzhao Zhou, Yan He, Tao Xu

et al.

Cell Research, Journal Year: 2024, Volume and Issue: 34(3), P. 214 - 231

Published: Feb. 8, 2024

Abstract Flickering light stimulation has emerged as a promising non-invasive neuromodulation strategy to alleviate neuropsychiatric disorders. However, the lack of neurochemical underpinning hampered its therapeutic development. Here, we demonstrate that flickering triggered an immediate and sustained increase (up 3 h after flickering) in extracellular adenosine levels primary visual cortex (V1) other brain regions, function frequency intensity, with maximal effects observed at 40 Hz 4000 lux. We uncovered cortical (glutamatergic GABAergic) neurons, rather than astrocytes, cellular source, intracellular generation from AMPK-associated energy metabolism pathways (but not SAM-transmethylation or salvage purine pathways), efflux mediated by equilibrative nucleoside transporter-2 (ENT2) molecular pathway responsible for generation. Importantly, 20 80 Hz) 30 min enhanced non-rapid eye movement (non-REM) REM sleep 2–3 mice. This somnogenic effect was abolished ablation V1 superior colliculus) neurons genetic deletion gene encoding ENT2 ENT1), but recaptured chemogenetic inhibition focal infusion into dose-dependent manner. Lastly, also promoted children insomnia decreasing onset latency, increasing total time, reducing waking onset. Collectively, our findings establish ENT2-mediated signaling basis flickering-induced unravel novel treatment insomnia, condition affects 20% world population.

Language: Английский

Citations

20
Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure DOI Creative Commons
Daniel Silverman, Changwan Chen, Shuang Chang

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(3)

Published: Jan. 17, 2025

Homeostatic sleep regulation is essential for optimizing the amount and timing of its revitalizing function, but mechanism underlying homeostasis remains poorly understood. Here, we show that optogenetic activation locus coeruleus (LC) noradrenergic neurons immediately increased propensity following a transient wakefulness, contrasting with many other arousal-promoting whose induces sustained wakefulness. Fiber photometry showed repeated or sensory stimulation caused rapid reduction calcium activity in LC steep declines noradrenaline/norepinephrine (NE) release both medial prefrontal cortex (mPFC). Knockdown α 2 A adrenergic receptors mitigated decline NE induced by repetitive extended demonstrating an important role receptor–mediated auto-suppression release. Together, these results suggest functional fatigue neurons, which reduces their wake-promoting capacity, contributes to pressure.

Language: Английский

Citations

3