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

A high-performance GRAB sensor reveals differences in the dynamics and molecular regulation between neuropeptide and neurotransmitter release DOI Creative Commons
Xiju Xia, Yulong Li

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 18, 2025

The co-existence and co-transmission of neuropeptides small molecule neurotransmitters within individual neuron represent a fundamental characteristic observed across various species. However, the differences regarding their in vivo spatiotemporal dynamics underlying molecular regulation remain poorly understood. Here, we develop GPCR-activation-based (GRAB) sensor for detecting short neuropeptide F (sNPF) with high sensitivity resolution. Furthermore, investigate between sNPF acetylcholine (ACh) from same neurons. Interestingly, our findings reveal distinct release ACh. Notably, results indicate that synaptotagmins (Syt) are involved these two processes, as Syt7 Sytα release, while Syt1 ACh release. Thus, this high-performance GRAB provides robust tool studying shedding insights into unique distinguish neurotransmitters.

Language: Английский

Citations

2
Microglia modulate stable wakefulness via the thalamic reticular nucleus in mice DOI Creative Commons
Hanxiao Liu, Xinxing Wang, Lu Chen

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 30, 2021

Abstract Microglia are important for brain homeostasis and immunity, but their role in regulating vigilance remains unclear. We employed genetic, physiological, metabolomic methods to examine microglial involvement the regulation of wakefulness sleep. Microglial depletion decreased stable nighttime mice by increasing transitions between non-rapid eye movement (NREM) Metabolomic analysis revealed that sleep-wake behavior closely correlated with diurnal variation ceramide, which disappeared microglia-depleted mice. Ceramide preferentially influenced microglia thalamic reticular nucleus (TRN), local TRN produced similar impaired wakefulness. Chemogenetic manipulations anterior neurons showed they regulated NREM Their firing capacity was suppressed both added ceramide. In mice, activating or inhibiting ceramide production restored These findings demonstrate can modulate through via signaling.

Language: Английский

Citations

73
A fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain DOI Creative Commons
Daisuke Ino, Yudai Tanaka, Hiroshi Hibino

et al.

Nature Methods, Journal Year: 2022, Volume and Issue: 19(10), P. 1286 - 1294

Published: Sept. 22, 2022

Abstract Oxytocin (OT), a hypothalamic neuropeptide that acts as neuromodulator in the brain, orchestrates variety of animal behaviors. However, relationship between brain OT dynamics and complex behaviors remains largely elusive, partly because lack suitable technique for its real-time recording vivo. Here, we describe MTRIA , G-protein-coupled receptor-based green fluorescent sensor has large dynamic range, affinity, ligand specificity orthologs, minimal effects on downstream signaling long-term fluorescence stability. By combining viral gene delivery fiber photometry-mediated measurements, demonstrate utility detection living mice. -mediated measurements indicate variability depending behavioral context physical condition an animal. will likely enable analysis physiological pathological processes.

Language: Английский

Citations

64
Fluorescence Imaging of Neural Activity, Neurochemical Dynamics, and Drug-Specific Receptor Conformation with Genetically Encoded Sensors DOI Open Access
Chunyang Dong, Yufeng Zheng,

Kiran Long-Iyer

et al.

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 273 - 294

Published: March 22, 2022

Recent advances in fluorescence imaging permit large-scale recording of neural activity and dynamics neurochemical release with unprecedented resolution behaving animals. Calcium highly optimized genetically encoded indicators provides a mesoscopic view from defined populations at cellular subcellular resolutions. Rigorously improved voltage sensors microscopy allow for robust spike populational neurons various brain regions. In addition, recent protein engineering efforts the past few years have led to development neurotransmitters neuromodulators. Here, we discuss applications these fluorescent reporting response behaviors different biological systems as well drug discovery. We also report simple model guide sensor selection optimization.

Language: Английский

Citations

63
The Role of Perioperative Sleep Disturbance in Postoperative Neurocognitive Disorders DOI Creative Commons
Xuan Wang,

Dongyu Hua,

Xiaole Tang

et al.

Nature and Science of Sleep, Journal Year: 2021, Volume and Issue: Volume 13, P. 1395 - 1410

Published: Aug. 1, 2021

Abstract: Postoperative neurocognitive disorder (PND) increases the length of hospital stay, mortality, and risk long-term cognitive impairment. Perioperative sleep disturbance is prevalent commonly ignored may increase PND. However, role perioperative disturbances in PND remains unclear. Nocturnal plays an indispensable learning, memory, maintenance cerebral microenvironmental homeostasis. Hospitalized also incidence postoperative delirium dysfunction. This review summarizes elucidates potential mechanisms underlying sleep-deprivation-mediated Activated neuroinflammation oxidative stress; impaired function blood-brain barrier glymphatic pathway; decreased hippocampal brain-derived neurotrophic factor, adult neurogenesis, sirtuin1 expression; accumulated amyloid-beta proteins are associated with individuals disorders. These findings suggest that improvement might reduce Future studies should further investigate Keywords: disturbance, impairment, delirium, dysfunction,

Language: Английский

Citations

58
A versatile GPCR toolkit to track in vivo neuromodulation: not a one-size-fits-all sensor DOI Creative Commons
Marie A. Labouesse, Tommaso Patriarchi

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 46(12), P. 2043 - 2047

Published: Feb. 18, 2021

Language: Английский

Citations

57
Locomotion activates PKA through dopamine and adenosine in striatal neurons DOI
Lei Ma, Julian Day‐Cooney, Omar Jáidar

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 762 - 768

Published: Nov. 9, 2022

Language: Английский

Citations

51
The Effects of Light and the Circadian System on Rhythmic Brain Function DOI Open Access
Charlotte von Gall

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2778 - 2778

Published: March 3, 2022

Life on earth has evolved under the influence of regularly recurring changes in environment, such as 24 h light/dark cycle. Consequently, organisms have developed endogenous clocks, generating (circadian) rhythms that serve to anticipate these rhythmic changes. In addition circadian rhythms, which persist constant conditions and can be entrained environmental light drives behavior brain function, especially nocturnal laboratory rodents. recent decades, research made great advances elucidation molecular clockwork perception. This review summarizes role clock with a focus complex interaction between different components mammalian system. Furthermore, chronodisruption consequence at night, genetic manipulation, neurodegenerative diseases is briefly discussed.

Language: Английский

Citations

47
Electron Conductive and Transparent Hydrogels for Recording Brain Neural Signals and Neuromodulation DOI Open Access
Quanduo Liang,

Zhenzhen Shen,

Xiguang Sun

et al.

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(9)

Published: Dec. 23, 2022

Recording brain neural signals and optogenetic neuromodulations open frontiers in decoding information neurodegenerative disease therapeutics. Conventional implantable probes suffer from modulus mismatch with biological tissues an irreconcilable tradeoff between transparency electron conductivity. Herein, a strategy is proposed to address these tradeoffs, which generates conductive transparent hydrogels polypyrrole-decorated microgels as cross-linkers. The optical of the electrodes can be attributed special structures that allow light waves bypass microgel particles minimize their interaction. Demonstrated by probing hippocampus rat brains, biomimetic electrode shows prolonged capacity for simultaneous neuromodulation recording signals. More importantly, intriguing brain-machine interaction realized, involves signal input brain, generation, controlling limb behaviors. This breakthrough work represents significant scientific advancement toward developing therapies.

Language: Английский

Citations

46
REM sleep is associated with distinct global cortical dynamics and controlled by occipital cortex DOI Creative Commons
Ziyue Wang, Xiang Fei, Xiaotong Liu

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 12, 2022

Abstract The cerebral cortex is spontaneously active during sleep, yet it unclear how this global cortical activity spatiotemporally organized, and whether such not only reflects sleep states but also contributes to state switching. Here we report that cortex-wide calcium imaging in mice revealed distinct stage-dependent spatiotemporal patterns of activity, modulation could regulate In particular, elevated activation the occipital regions (including retrosplenial visual areas) became dominant rapid-eye-movement (REM) sleep. Furthermore, pontogeniculooccipital (PGO) wave-like was associated with transitions REM optogenetic inhibition strongly promoted deep by suppressing NREM-to-REM transition. Thus, whereas subcortical networks are critical for initiating maintaining wakefulness states, plays an role controlling states.

Language: Английский

Citations

42