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

Revealing the contribution of astrocytes to glutamatergic neuronal transmission DOI Creative Commons
Ares Orlando Cuellar-Santoyo, Victor Manuel Ruiz-Rodríguez,

Teresa Belem Mares-Barbosa

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Jan. 19, 2023

Research on glutamatergic neurotransmission has focused mainly the function of presynaptic and postsynaptic neurons, leaving astrocytes with a secondary role only to ensure successful neurotransmission. However, recent evidence indicates that contribute actively even regulate neuronal transmission at different levels. This review establishes framework by comparing components between neurons examine how modulate or otherwise influence transmission. We have included most findings about in neurotransmission, allowing us understand complex network neuron-astrocyte interactions. despite knowledge synaptic modulation astrocytes, their contribution specific physiological pathological conditions remains be elucidated. A full understanding astrocyte's processing could open fruitful new frontiers development therapeutic applications.

Language: Английский

Citations

38
Functions of Astrocytes under Normal Conditions and after a Brain Disease DOI Open Access
Soraya L. Vallés, Sandeep Kumar Singh,

Juan Campos-Campos

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8434 - 8434

Published: May 8, 2023

In the central nervous system (CNS) there are a greater number of glial cells than neurons (between five and ten times more). Furthermore, they have functions (more eight functions). Glia comprises different types cells, those neural origin (astrocytes, radial glia, oligodendroglia) differentiated blood monocytes (microglia). During ontogeny, develop earlier (at fetal day 15 in rat) astrocytes later 21 rat), which could indicate their important crucial role CNS. Analysis phylogeny reveals that reptiles lower compared to humans this is reversed, as neurons. These data perhaps imply special involved many vital functions, including memory, learning processes. addition, mechanisms protect CNS through production antioxidant anti-inflammatory proteins clean extracellular environment help communicate correctly with each other. The inflammatory mediators prevent changes brain homeostasis. On contrary, excessive, or continued appears characteristic element diseases, such Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple (MS), neurodevelopmental bipolar disorder, schizophrenia, autism. drugs techniques been developed reverse oxidative stress and/or excess inflammation occurs but much remains be investigated. This review attempts highlight functional relevance normal neuropathological conditions by showing molecular cellular

Language: Английский

Citations

32
Pathology and Astrocytes in Autism DOI Creative Commons

Gelareh Vakilzadeh,

Verónica Martínez‐Cerdeño

Neuropsychiatric Disease and Treatment, Journal Year: 2023, Volume and Issue: Volume 19, P. 841 - 850

Published: April 1, 2023

Abstract: A distinct pathology for autism spectrum disorder (ASD) remains elusive. Human and animal studies have focused on investigating the role of neurons in ASD. However, recent hinted that glial cell could be a characteristic Astrocytes are most abundant brain play an important neuronal function, both during development adult. They regulate migration, dendritic spine development, control concentration neurotransmitters at synaptic cleft. also responsible synaptogenesis, function. Therefore, any change astrocyte number and/or function contribute to impairment connectivity has been reported Data available date is scarce but indicates while astrocytes reduced, their state activation GFAP expression increased Disruption ASD may affect proper neurotransmitter metabolism, inflammation. alterations common other neurodevelopmental disorders. Future about required better understand this disorder. Keywords: autism, astrocyte, postmortem,

Language: Английский

Citations

28
Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia DOI

Xue‐Jing Lv,

Su‐Su Lv,

Guohong Wang

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 224 - 241

Published: Jan. 18, 2024

Language: Английский

Citations

9
Cortical astrocyte N-methyl-D-aspartate receptors influence whisker barrel activity and sensory discrimination in mice DOI Creative Commons
Noushin Ahmadpour, Meher Kantroo, Michael Stobart

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 21, 2024

Astrocytes express ionotropic receptors, including N-methyl-D-aspartate receptors (NMDARs). However, the contribution of NMDARs to astrocyte-neuron interactions, particularly in vivo, has not been elucidated. Here we show that a knockdown approach selectively reduce mouse cortical astrocytes decreases astrocyte Ca

Language: Английский

Citations

9
An astroglial basis of major depressive disorder: Molecular, Cellular, and Circuit Features DOI
Chenglin Lu, Jing Ren, Xiong Cao

et al.

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Language: Английский

Citations

9
Calcium‐Dependent Signaling in Astrocytes: Downstream Mechanisms and Implications for Cognition DOI
Alexandra Veiga, Daniela Sofia Abreu, José Duarte Dias

et al.

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(2)

Published: Feb. 1, 2025

Astrocytes are glial cells recognized for their diverse roles in regulating brain circuit structure and function. They can sense adapt to changes the microenvironment due unique structural biochemical properties. A key aspect of astrocytic function involves calcium (Ca2+)-dependent signaling, which serves as a fundamental mechanism interactions with neurons other brain. However, while significant progress has been made understanding spatio-temporal properties Ca2+ signals, downstream molecular pathways exact mechanisms through astrocytes decode these signals regulate homeostatic physiological processes remain poorly understood. To address this topic, we review here available literature on sources intracellular Ca2+, well its signaling pathways. We well-studied Ca2+-dependent exocytosis but draw attention additional that less understood are, most likely, highly influential many cellular functions. Finally, how is thought underlie neuron-astrocyte regions involved cognitive processing.

Language: Английский

Citations

1
Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits DOI Creative Commons
Loïc Binan, Aiping Jiang,

Serwah Danquah

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Highlights•Perturb-FISH combines spatial transcriptomics and readout of CRISPR perturbation•We recover the effects genetic perturbation on transcriptome single cells•We find specific networks related to cell neighbors in tissue•We connect time-resolved imaging phenotypes after perturbationSummaryPooled optical screens have enabled study cellular interactions, morphology, or dynamics at massive scale, but they not yet leveraged power highly plexed single-cell resolved transcriptomic readouts inform molecular pathways. Here, we present a combination with parallel detection situ amplified guide RNAs (Perturb-FISH). Perturb-FISH recovers intracellular that are consistent RNA-sequencing-based (Perturb-seq) screen lipopolysaccharide response cultured monocytes, it uncovers intercellular density-dependent regulation innate immune response. Similarly, three-dimensional xenograft models, identifies tumor-immune interactions altered by knockout. When paired functional separate autism spectrum disorder risk genes human-induced pluripotent stem (hIPSC) astrocytes, shows common calcium activity their associated dysregulated is thus general method for studying associations biology resolution.Graphical abstract

Language: Английский

Citations

1
Modeling human neurodevelopmental diseases with brain organoids DOI Creative Commons

Xiaoxiang Lu,

Jiajie Yang,

Yangfei Xiang

et al.

Cell Regeneration, Journal Year: 2022, Volume and Issue: 11(1)

Published: Jan. 4, 2022

Abstract Studying the etiology of human neurodevelopmental diseases has long been a challenging task due to brain’s complexity and its limited accessibility. Human pluripotent stem cells (hPSCs)-derived brain organoids are capable recapitulating various features functionalities brain, allowing investigation intricate pathogenesis developmental abnormalities. Over past years, have facilitated identifying disease-associated phenotypes underlying mechanisms for diseases. Integrating with more cutting-edge technologies, particularly gene editing, further empower disease modeling. Here, we review latest progress in modeling disorders organoids.

Language: Английский

Citations

34
Simultaneous CRISPR screening and spatial transcriptomics reveals intracellular, intercellular, and functional transcriptional circuits DOI Creative Commons
Loïc Binan,

Serwah Danquah,

Vera Valakh

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 1, 2023

Pooled optical screens have enabled the study of cellular interactions, morphology, or dynamics at massive scale, but not yet leveraged power highly-plexed single-cell resolved transcriptomic readouts to inform molecular pathways. Here, we present Perturb-FISH, which bridges these approaches by combining imaging spatial transcriptomics with parallel detection in situ amplified guide RNAs. We show that Perturb-FISH recovers intracellular effects are consistent Perturb-seq results a screen lipopolysaccharide response cultured monocytes, and uncover new intercellular density-dependent regulation innate immune response. further pair functional readout autism spectrum disorder risk genes, showing common calcium activity phenotypes induced pluripotent stem cell derived astrocytes their associated genetic interactions dysregulated is thus generally applicable method for studying associations biology resolution.

Language: Английский

Citations

18