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

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 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.

Язык: Английский

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

и другие.

Nature reviews. Neuroscience, Год журнала: 2022, Номер 23(5), С. 257 - 274

Опубликована: Март 31, 2022

Язык: Английский

Процитировано

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

и другие.

Neuron, Год журнала: 2021, Номер 110(5), С. 770 - 782.e5

Опубликована: Дек. 22, 2021

Язык: Английский

Процитировано

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

и другие.

Nature Biotechnology, Год журнала: 2021, Номер 40(5), С. 787 - 798

Опубликована: Ноя. 11, 2021

Язык: Английский

Процитировано

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

и другие.

Journal of Sleep Research, Год журнала: 2022, Номер 31(4)

Опубликована: Май 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

Язык: Английский

Процитировано

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

и другие.

Nature Biotechnology, Год журнала: 2023, Номер 41(7), С. 944 - 957

Опубликована: Янв. 2, 2023

Язык: Английский

Процитировано

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

и другие.

Neuron, Год журнала: 2023, Номер 112(5), С. 718 - 739

Опубликована: Дек. 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.

Язык: Английский

Процитировано

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

Trends in Neurosciences, Год журнала: 2023, Номер 46(3), С. 228 - 239

Опубликована: Янв. 10, 2023

Язык: Английский

Процитировано

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

Chenyan Ma,

Bing Li, Daniel Silverman

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(2), С. 249 - 258

Опубликована: Янв. 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

Язык: Английский

Процитировано

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

и другие.

Cell Research, Год журнала: 2024, Номер 34(3), С. 214 - 231

Опубликована: Фев. 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.

Язык: Английский

Процитировано

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

и другие.

Science Advances, Год журнала: 2025, Номер 11(3)

Опубликована: Янв. 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.

Язык: Английский

Процитировано

3