Neuronal activity-induced, equilibrative nucleoside transporter-dependent, somatodendritic adenosine release revealed by a GRAB sensor

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(14)

Опубликована: Март 30, 2023

The purinergic signaling molecule adenosine (Ado) modulates many physiological and pathological functions in the brain. However, exact source of extracellular Ado remains controversial. Here, utilizing a newly optimized genetically encoded GPCR-Activation-Based fluorescent sensor (GRABAdo), we discovered that neuronal activity-induced elevation is due to direct release from somatodendritic compartments neurons, rather than axonal terminals, hippocampus. Pharmacological genetic manipulations reveal depends on equilibrative nucleoside transporters but not conventional vesicular mechanisms. Compared with fast-vesicular glutamate release, slow (~40 s) requires calcium influx through L-type channels. Thus, this study reveals an activity-dependent second-to-minute local potentially serving modulatory as retrograde signal.

Язык: Английский

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Adenosine-independent regulation of the sleep–wake cycle by astrocyte activity

Cell Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Фев. 7, 2023

Astrocytes play a crucial role in regulating sleep-wake behavior, and adenosine signaling is generally thought to be involved. Here we show multiple lines of evidence supporting that modulation the behavior by astrocyte Ca2+ activity could occur without signaling. In basal forebrain brainstem, two brain regions are known essential for regulation, chemogenetically-induced elevation significantly modulated cycle. Although level positively correlated with amount extracellular adenosine, as revealed genetically encoded sensor, found no detectable change after suppressing elevation, transgenic mice lacking one major ATP-adenosine conversion enzymes showed similar Ca2+-induced sleep modulation. Furthermore, dependent primarily on local neuronal activity, causing region-specific regulation Thus, neural activity-dependent regulate independent

Язык: Английский

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Advanced near‐infrared light approaches for neuroimaging and neuromodulation

BMEMat, Год журнала: 2023, Номер 1(2)

Опубликована: Май 5, 2023

Abstract Almost all physiological processes of animals are controlled by the brain, including language, cognitive, memory, learning, emotion and so forth. Minor brain dysfunction usually leads to diseases disorders. Therefore, it' is greatly meaningful urgent for scientists have a better understanding structure function. Optical approaches can provide powerful tools imaging modulating brain. In particular, optical in near‐infrared (NIR) window (700–1700 nm) exhibit excellent prosperities deep tissue penetration low scattering absorption compared with those visible windows (400–700 nm), which provides promising approach develop desired methods neuroimaging neuromodulation tissues. this review, variable types NIR light neural ions, membrane potential, neurotransmitters, other critical molecules functions summarized. latest breakthrough research regulation NIR‐II (1000–1700 highlighted. Finally, we conclude challenges prospects light‐based both basic further clinical translation.

Язык: Английский

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Evidence that Alzheimer’s Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry

Journal of Alzheimer s Disease, Год журнала: 2024, Номер 99(2), С. 447 - 470

Опубликована: Апрель 23, 2024

Mounting evidence indicates that a physiological function of amyloid-β (Aβ) is to mediate neural activity-dependent homeostatic and competitive synaptic plasticity in the brain. I have previously summarized lines supporting this hypothesis highlighted similarities between Aβ anti-microbial peptides mediating cell/synapse competition. In cell competition, deploy multitude mechanisms ensure both self-protection competitor elimination. Here review recent studies showing similar are at play Aβ-mediated synapse competition perturbations these underpin Alzheimer’s disease (AD). Specifically, discuss ApoE, two crucial players AD, co-operate regulation Glial ApoE promotes by increasing production trophic monomeric inhibiting its assembly into toxic oligomers. Conversely, oligomers, once assembled, promote elimination synapses via direct activity amplification “eat-me” signals promoting weak synapses. further summarize neuronal may be part gene regulatory network normally plasticity, explaining selective vulnerability expressing neurons AD brains. Lastly, sleep key Aβ-orchestrated which not only induced but also required for underlining link AD. Together, results strongly argue gone awry, novel perspective research.

Язык: Английский

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Adenosine triggers early astrocyte reactivity that provokes microglial responses and drives the pathogenesis of sepsis-associated encephalopathy in mice

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

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