Spontaneous and multifaceted ATP release from astrocytes at the scale of hundreds of synapses DOI
Yoshiki Hatashita, Zhaofa Wu, Hirotaka Fujita

et al.

Glia, Journal Year: 2023, Volume and Issue: 71(9), P. 2250 - 2265

Published: June 1, 2023

Abstract Astrocytes participate in information processing by releasing neuroactive substances termed gliotransmitters, including ATP. Individual astrocytes come into contact with thousands of synapses their ramified structure, but the spatiotemporal dynamics ATP gliotransmission remains unclear, especially physiological brain tissue. Using a genetically encoded fluorescent sensor, GRAB ATP1.0 , we discovered that extracellular increased locally and transiently absence stimuli neuron–glia co‐cultures, cortical slices, anesthetized mouse brain. Spontaneous release events were tetrodotoxin‐insensitive suppressed gliotoxin, fluorocitrate, typically spread over 50–250 μm 2 area at concentrations capable activating purinergic receptors. Besides, most did not coincide Ca 2+ transients, intracellular buffering BAPTA‐AM affect event frequency. Clustering analysis revealed these followed multiple distinct kinetics, blockade exocytosis only decreased minor group slow events. Overall, spontaneously through mechanisms, mainly non‐vesicular ‐independent manners, thus potentially regulating hundreds all together.

Language: Английский

The ATP Level in the Medial Prefrontal Cortex Regulates Depressive-like Behavior via the Medial Prefrontal Cortex-Lateral Habenula Pathway DOI
Song Lin, Lang Huang,

Zhou-Cai Luo

et al.

Biological Psychiatry, Journal Year: 2022, Volume and Issue: 92(3), P. 179 - 192

Published: Feb. 22, 2022

Language: Английский

Citations

81
Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells DOI Creative Commons
Yao Liu, Xi Shen, Yuhan Zhang

et al.

Glia, Journal Year: 2023, Volume and Issue: 71(6), P. 1383 - 1401

Published: Feb. 17, 2023

Abstract The mammalian brain is a complex organ comprising neurons, glia, and more than 1 × 10 14 synapses. Neurons are heterogeneous group of electrically active cells, which form the framework circuitry brain. However, glial primarily divided into astrocytes, microglia, oligodendrocytes (OLs), oligodendrocyte precursor cells (OPCs), constitute approximately half all neural in central nervous system (CNS) mainly provide nutrition tropic support to neurons In last two decades, concept “tripartite synapses” has drawn great attention, emphasizes that astrocytes an integral part synapse regulate neuronal activity feedback manner after receiving signals. Since then, synaptic modulation by been extensively studied substantially revised. this review, we summarize latest significant findings on how particular, microglia OL lineage impact remodel structure function synapses Our review highlights cellular molecular aspects neuron‐glia crosstalk provides additional information aberrant communication between glia may contribute pathologies.

Language: Английский

Citations

73
Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder DOI Creative Commons

Yue Xiong,

Jianhui Chen, Yingbo Li

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 20, 2023

Autism spectrum disorder (ASD) is a common neurodevelopmental with onset in childhood. The mechanisms underlying ASD are unclear. In recent years, the role of microglia and astrocytes has received increasing attention. Microglia prune synapses or respond to injury by sequestrating site expressing inflammatory cytokines. Astrocytes maintain homeostasis brain microenvironment through uptake ions neurotransmitters. However, molecular link between and, remains unknown. Previous research shown significant ASD, reports increased numbers reactive postmortem tissues animal models ASD. Therefore, an enhanced understanding roles essential for developing effective therapies. This review aimed summarize functions their contributions

Language: Английский

Citations

47
Astrocyte metabolism and signaling pathways in the CNS DOI Creative Commons
Yong-Mei Zhang, Yingbei Qi,

Ya-nan Gao

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 4, 2023

Astrocytes comprise half of the cells in central nervous system and play a critical role maintaining metabolic homeostasis. Metabolic dysfunction astrocytes has been indicated as primary cause neurological diseases, such depression, Alzheimer’s disease, epilepsy. Although functionalities are well known, their relationship to disorders is poorly understood. The ways which regulate metabolism glucose, amino acids, lipids have all implicated diseases. Metabolism also exhibited significant influence on neuron functionality brain’s neuro-network. In this review, we focused processes present astrocytes, most notably glucose pathway, fatty acid amino-acid pathway. For metabolism, glycolysis pentose-phosphate oxidative phosphorylation followed oxidation, ketone body sphingolipid metabolism. summarized neurotransmitter serine kynurenine pathways. This review will provide an overview functional changes astrocyte overall perspective current treatment therapy for disorders.

Language: Английский

Citations

45
The Impact of Microglia on Neurodevelopment and Brain Function in Autism DOI Creative Commons

Yuyi Luo,

Zhengbo Wang

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 210 - 210

Published: Jan. 17, 2024

Microglia, as one of the main types glial cells in central nervous system (CNS), are widely distributed throughout brain and spinal cord. The normal number function microglia very important for maintaining homeostasis CNS. In recent years, scientists have paid widespread attention to role Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder, patients with ASD severe deficits behavior, social skills, communication. Most previous studies on focused neuronal pathological changes, such increased cell proliferation, accelerated differentiation, impaired synaptic development, reduced spontaneous synchronous activity. Currently, more research has found that microglia, immune cells, can promote neurogenesis pruning maintain CNS homeostasis. They usually reduce unnecessary connections early life. Some researchers proposed many phenotypes may be caused by microglial abnormalities. Based this, we summarize ASD, focusing We aim clarify essential factors influenced explore possibility microglia-related pathways potential targets ASD.

Language: Английский

Citations

20
Glial Perturbation in Metal Neurotoxicity: Implications for Brain Disorders DOI Creative Commons
Olayemi K. Ijomone, Ukwubile Ileje Inelo, Vivian O. Aneke

et al.

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 4 - 4

Published: Jan. 6, 2025

Overexposure of humans to heavy metals and essential poses a significant risk for the development neurological neurodevelopmental disorders. The mechanisms through which these exert their effects include generation reactive oxygen species, mitochondrial dysfunction, activation inflammatory pathways, disruption cellular signaling. function glial cells in brain maintenance homeostasis cannot be overlooked. are particularly susceptible metal-induced neurotoxicity. Accumulation promotes microglial activation, triggering responses that can coincide with other neurotoxicity, inducing alteration synaptic transmission, cognitive deficit, neuronal damage. In this review, we highlighted role dysfunction some selected neurodegenerative diseases We further dive into how exposure such as nickel, manganese, methyl mercury, cadmium, iron, arsenic, lead affect functions microglia, astrocytes, oligodendrocytes they on relation Potential therapeutic interventions use new improved chelating agents antioxidant therapies might approach alleviating perturbations.

Language: Английский

Citations

3
Artemisinin Alleviates Astrocyte Overactivation and Neuroinflammation by Modulating the IRE1/NF-κB Signaling Pathway in In Vitro and In Vivo Alzheimer's Disease Models DOI
Lei Chen, Xia Zhao, Rui Sheng

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 229, P. 96 - 110

Published: Jan. 16, 2025

Language: Английский

Citations

2
Astrocytes and major depression: The purinergic avenue DOI
Yafei Zhao, Alexei Verkhratsky, Yong Tang

et al.

Neuropharmacology, Journal Year: 2022, Volume and Issue: 220, P. 109252 - 109252

Published: Sept. 16, 2022

Language: Английский

Citations

46
Dopamine activates astrocytes in prefrontal cortex via α1-adrenergic receptors DOI Creative Commons
Silvia Pittolo, Sae Yokoyama,

Drew D. Willoughby

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 40(13), P. 111426 - 111426

Published: Sept. 1, 2022

The prefrontal cortex (PFC) is a hub for cognitive control, and dopamine profoundly influences its functions. In other brain regions, astrocytes sense diverse neurotransmitters neuromodulators and, in turn, orchestrate regulation of neuroactive substances. However, basic physiology PFC astrocytes, including which neuromodulatory signals they respond to how contribute function, unclear. Here, we characterize divergent signaling signatures mouse the primary sensory cortex, show differential responsiveness locomotion. We find that express receptors but are unresponsive through Gs/Gi-cAMP pathway. Instead, fast calcium time locked release mediated by α1-adrenergic both ex vivo vivo. Further, describe dopamine-triggered extracellular ATP at astrocyte territories. Thus, identify as active players dopaminergic PFC, contributing function though neuromodulator receptor crosstalk.

Language: Английский

Citations

43
Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression DOI Creative Commons
Jiaming Liu,

Jia‐Wen Mo,

Xunda Wang

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(46)

Published: Nov. 16, 2022

Major depressive disorder (MDD) is a devastating mental that affects up to 17% of the population worldwide. Although brain-wide network-level abnormalities in MDD patients via resting-state functional magnetic resonance imaging (rsfMRI) exist, mechanisms underlying these network changes are unknown, despite their immense potential for depression diagnosis and management. Here, we show astrocytic calcium-deficient mice, inositol 1,4,5-trisphosphate-type-2 receptor knockout mice ( Itpr2 −/− mice), display abnormal rsfMRI connectivity (rsFC) depression-related networks, especially decreased rsFC medial prefrontal cortex (mPFC)–related pathways. We further uncover decreases highly consistent with those mPFC-related Optogenetic activation mPFC astrocytes partially enhances networks both wild-type mice. neurons or mPFC-striatum pathway rescues disrupted depressive-like behaviors Our results identify previously unknown role astrocyte dysfunction driving depression.

Language: Английский

Citations

41