Cortical astrocyte activation triggers meningeal nociception and migraine-like pain DOI Creative Commons
Dara Bree, Jun Zhao, Jennifer Stratton

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Migraine attacks are believed to originate in the brain, but exact mechanisms by which brain generates peripheral nociceptive signals that drive migraine pain remain unclear. Sensory cortex hyperexcitability has been observed consistently across different subtypes. Astrocytes detect aberrant increases cortical activity via their Gq-coupled receptors and respond releasing gliotransmitters other factors with pro-inflammatory properties. In present study, we used a rat model investigate whether heightened astrocyte signaling is sufficient trigeminal meningeal responses linked generation of headaches. We an AAV-based chemogenetic approach allows selective activation Gq-GPCR signaling. targeted astrocytes visual as this region implicated migraine. Furthermore, meninges overlying densely innervated fibers. combined vivo single-unit recording nociceptors assess changes ongoing mechanosensitivity, along testing migraine-like behaviors. further calcitonin gene-related peptide (CGRP), using monoclonal antibody (anti-CGRP mAb), relevance discovered drives persistent discharge increased mechanosensitivity nociceptors. Cortical astrocytic also generated cephalic mechanical hypersensitivity, reduced exploratory behavior, anxiety-like behaviors Blocking suppressed astrocyte-mediated nociceptor alleviated associated migraine-related Our findings reveal previously unappreciated role for augmented triggering factor generate nociception greatly expand our understanding pathophysiology.

Язык: Английский

Timing to be precise? An overview of spike timing-dependent plasticity, brain rhythmicity, and glial cells interplay within neuronal circuits DOI Creative Commons
Yuniesky Andrade‐Talavera, André Fisahn, Antonio Rodríguez Moreno

и другие.

Molecular Psychiatry, Год журнала: 2023, Номер 28(6), С. 2177 - 2188

Опубликована: Март 29, 2023

Abstract In the mammalian brain information processing and storage rely on complex coding decoding events performed by neuronal networks. These actions are based computational ability of neurons their functional engagement in assemblies where precise timing action potential firing is crucial. Neuronal circuits manage a myriad spatially temporally overlapping inputs to compute specific outputs that proposed underly memory traces formation, sensory perception, cognitive behaviors. Spike-timing-dependent plasticity (STDP) electrical rhythms suggested underlie such functions while physiological evidence assembly structures mechanisms driving both processes continues be scarce. Here, we review foundational current precision cooperative activity STDP rhythms, interactions, emerging role glial cells processes. We also provide an overview correlates discuss limitations controversies, future perspectives experimental approaches, application humans.

Язык: Английский

Процитировано

33
Astrocytes as master modulators of neural networks: Synaptic functions and disease‐associated dysfunction of astrocytes DOI Creative Commons
Jeffrey A. Stogsdill, Corey C. Harwell, Steven A. Goldman

и другие.

Annals of the New York Academy of Sciences, Год журнала: 2023, Номер 1525(1), С. 41 - 60

Опубликована: Май 23, 2023

Abstract Astrocytes are the most abundant glial cell type in central nervous system and essential to development, plasticity, maintenance of neural circuits. heterogeneous, with their diversity rooted developmental programs modulated by local brain environment. play integral roles regulating coordinating activity extending far beyond metabolic support neurons other phenotypes. Both gray white matter astrocytes occupy critical functional niches capable modulating physiology on time scales slower than synaptic but faster those adaptive responses requiring a structural change or myelination. Given many associations roles, it is not surprising that astrocytic dysfunction has been causally implicated broad set neurodegenerative neuropsychiatric disorders. In this review, we focus recent discoveries concerning contributions function networks, dual contribution development maturation, role supporting myelin integrity, hence conduction its regulation. We then address emerging disease pathogenesis potential strategies for targeting these cells therapeutic purposes.

Язык: Английский

Процитировано

25
Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury DOI Creative Commons
Wojciech Czyżewski, Marek Mazurek, Leon Sakwa

и другие.

Cells, Год журнала: 2024, Номер 13(2), С. 148 - 148

Опубликована: Янв. 12, 2024

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents central nervous system (CNS), in both pathophysiology and possible rehabilitation TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) neuroprotective (A2) phenotypes. paper elucidates interactions with neurons, their role neuroinflammation, potential for exploitation. Emphasized strategies encompass utilization endocannabinoid calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, innovative technique astrocyte transplantation as means to repair damaged neural tissues.

Язык: Английский

Процитировано

10
Astrocyte switch to the hyperactive mode DOI Creative Commons

Shun ARAKI,

Ichinosuke Onishi,

Yoko Ikoma

и другие.

Glia, Год журнала: 2024, Номер 72(8), С. 1418 - 1434

Опубликована: Апрель 9, 2024

Abstract Increasing pieces of evidence have suggested that astrocyte function has a strong influence on neuronal activity and plasticity, both in physiological pathophysiological situations. In epilepsy, astrocytes been shown to respond epileptic seizures; however, whether they can act as trigger for seizures not determined. Here, using the copper implantation method, spontaneous hyperactivity episodes were reliably induced during week following implantation. With near 24‐h continuous recording over 1 local field potential with vivo electrophysiology cytosolic Ca 2+ fiber photometry occurrences seizure captured. Approximately day after implantation, isolated aberrant events often observed before accompanied by hyperactivity, suggesting role epileptogenesis. Within single developed episode, increase preceded ~20 s, actions originating from could be occurrence seizures. Astrocyte‐specific stimulation channelrhodopsin‐2 or deep‐brain direct current was capable inducing hyperactivity. Injection an astrocyte‐specific metabolic inhibitor, fluorocitrate, able significantly reduce magnitude spontaneously occurring These results suggest triggering individual reciprocal astrocyte‐neuron interactions likely amplify exacerbate Therefore, future epilepsy treatment targeted at achieve control.

Язык: Английский

Процитировано

10
A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice DOI Creative Commons
Ignacio Fernández‐Moncada, Gianluca Lavanco,

Unai B. Fundazuri

и другие.

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

Опубликована: Авг. 9, 2024

Astrocytes control brain activity via both metabolic processes and gliotransmission, but the physiological links between these functions are scantly known. Here we show that endogenous activation of astrocyte type-1 cannabinoid (CB1) receptors determines a shift glycolysis towards lactate-dependent production D-serine, thereby gating synaptic cognitive in male mice. Mutant mice lacking CB1 receptor gene astrocytes (GFAP-CB1-KO) impaired novel object recognition (NOR) memory. This phenotype is rescued by gliotransmitter its precursor L-serine, also lactate 3,5-DHBA, an agonist HCAR1. Such effect abolished when astrocyte-specific phosphorylated-pathway (PP), which diverts L-serine synthesis, blocked. Consistently, 3,5-DHBA promoted co-agonist binding site occupancy CA1 post-synaptic NMDA hippocampal slices PP-dependent manner. Thus, tight cross-talk astrocytic energy metabolism gliotransmission processes.

Язык: Английский

Процитировано

10
In vivo Calcium Extrusion from Accumbal Astrocytes Reduces Anxiety-like Behaviors but Increases Compulsive-like Responses and Compulsive ethanol drinking in Mice DOI
Lee Peyton, Hamied Haroon, Anthony D. Umpierre

и другие.

Neuropharmacology, Год журнала: 2025, Номер 268, С. 110320 - 110320

Опубликована: Янв. 20, 2025

Язык: Английский

Процитировано

2
Astrocyte structural heterogeneity in the mouse hippocampus DOI Creative Commons
João Filipe Viana, João Luís Machado, Daniela Sofia Abreu

и другие.

Glia, Год журнала: 2023, Номер 71(7), С. 1667 - 1682

Опубликована: Март 22, 2023

Abstract Astrocytes are integral components of brain circuits, where they sense, process, and respond to surrounding activity, maintaining homeostasis regulating synaptic transmission, the sum which results in behavior modulation. These interactions possible due their complex morphology, composed a tree‐like structure processes cover defined territories ramifying mesh‐like system fine leaflets unresolved by conventional optic microscopy. While recent reports devoted more attention dynamic with synapses, our knowledge about “backbone” physiological conditions is incomplete. Recent transcriptomic studies described astrocyte molecular diversity, suggesting structural heterogeneity regions such as hippocampus, crucial for cognitive emotional behaviors. In this study, we carried out analysis astrocytes across hippocampal subfields Cornu Ammonis area 1 (CA1) dentate gyrus dorsoventral axis. We found that display subfields, conserved along further appear contribute an exocytosis‐dependent manner signaling loop maintains backbone structure. findings reveal appears follow layer‐specific cues depend on neuro‐glial environment.

Язык: Английский

Процитировано

22
Dynamic Image Representation in a Spiking Neural Network Supplied by Astrocytes DOI Creative Commons
Sergey V. Stasenko, Victor Kazantsev

Mathematics, Год журнала: 2023, Номер 11(3), С. 561 - 561

Опубликована: Янв. 20, 2023

The mathematical model of the spiking neural network (SNN) supplied by astrocytes is investigated. are a specific type brain cells which not electrically excitable but induce chemical modulations neuronal firing. We analyze how influence images encoded in form dynamic pattern SNN. Serving at much slower time scale, astrocytic interacting with neurons can remarkably enhance image representation quality. dynamics affected noise distorting information image. demonstrate that activation significantly suppress influence, improving

Язык: Английский

Процитировано

20
Multifarious astrocyte–neuron dialog in shaping neural circuit architecture DOI
Khai Huynh Ngoc,

Younghyeon Jeon,

Jaewon Ko

и другие.

Trends in Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Июнь 1, 2024

Язык: Английский

Процитировано

8
The role of astrocyte metabolic reprogramming in ischemic stroke (Review) DOI Creative Commons
Weixin Chen, Tangyou Mao, Rui Ma

и другие.

International Journal of Molecular Medicine, Год журнала: 2025, Номер 55(3)

Опубликована: Янв. 21, 2025

Ischemic stroke, a leading cause of disability and mortality worldwide, is characterized by the sudden loss blood flow in specific area brain. Intravenous thrombolysis with recombinant tissue plasminogen activator only approved pharmacological treatment for acute ischemic stroke; however, aforementioned has significant clinical limitations, thus there an urgent need development novel mechanisms therapeutic strategies stroke. Astrocytes, abundant versatile cells central nervous system, offer crucial support to neurons nutritionally, structurally physically. They also contribute blood‑brain barrier formation regulate neuronal extracellular ion concentrations. Accumulated evidence revealed involvement astrocytes regulation host neurotransmitter metabolism, immune response repair, different metabolic characteristics can process suggesting that targeted astrocyte reprogramming may prognosis In present review, current understanding multifaceted along its regulatory factors pathways, as well promote polarization balance, which hold promise immunometabolism‑targeted therapies were summarized.

Язык: Английский

Процитировано

1