Spontaneous and multifaceted <scp>ATP</scp> release from astrocytes at the scale of hundreds of synapses

Hatashita, Yoshiki; Z, Wu; Fujita, Hirotaka; Kumamoto, Takuma; Livet, Jean; Li, Yulong; Tanifuji, Manabu; Inoue, Takafumi

doi:10.1002/glia.24392

Cited by 5 publications

(6 citation statements)

References 84 publications

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“…Serum-deprivation lowered both ATP and CrP levels in cultured astrocytes, suggesting that serum contains compounds which support the maintenance of high cellular levels of both compounds. A loss in cellular ATP and CrP of astrocytes under such conditions is not unexpected as some cellular CrP is likely to disappear by spontaneous formation of creatinine [ 57 ] and as ATP can be exported from astrocytes [ 58 , 59 ]. Serum components may be used by astrocytes to compensate for these losses.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Cellular Levels of Adenosine Phosphates and Creatine Phosphate in Cultured Primary Astrocytes

Karger,

Berger,

Dringen

2023

Neurochem Res

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Adenosine triphosphate (ATP) is the main energy currency of all cells, while creatine phosphate (CrP) is considered as a buffer of high energy-bond phosphate that facilitates rapid regeneration of ATP from adenosine diphosphate (ADP). Astrocyte-rich primary cultures contain ATP, ADP and adenosine monophosphate (AMP) in average specific contents of 36.0 ± 6.4 nmol/mg, 2.9 ± 2.1 nmol/mg and 1.7 ± 2.1 nmol/mg, respectively, which establish an adenylate energy charge of 0.92 ± 0.04. The average specific cellular CrP level was found to be 25.9 ± 10.8 nmol/mg and the CrP/ATP ratio was 0.74 ± 0.28. The specific cellular CrP content, but not the ATP content, declined with the age of the culture. Absence of fetal calf serum for 24 h caused a partial loss in the cellular contents of both CrP and ATP, while application of creatine for 24 h doubled the cellular CrP content and the CrP/ATP ratio, but did not affect ATP levels. In glucose-deprived astrocytes, the high cellular ATP and CrP contents were rapidly depleted within minutes after application of the glycolysis inhibitor 2-deoxyglucose and the respiratory chain inhibitor antimycin A. For those conditions, the decline in CrP levels always preceded that of ATP contents. In contrast, incubation of glucose-fed astrocytes for up to 30 min with antimycin A had little effect on the high cellular ATP content, while the CrP level was significantly lowered. These data demonstrate the importance of cellular CrP for maintaining a high cellular ATP content in astrocytes during episodes of impaired ATP regeneration.

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Section: Discussionmentioning

confidence: 99%

Modulation of Cellular Levels of Adenosine Phosphates and Creatine Phosphate in Cultured Primary Astrocytes

Karger,

Berger,

Dringen

2023

Neurochem Res

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“…GRAB ADO1.0 permits analysis of adenosine dynamics in the sleep–wake cycle by in vivo fiber photometry ( Peng et al, 2020 ). GRAB ATP1.0 expressed in astrocytes detects the spontaneous release of ATP, some of which seems to occur locally ( Hatashita et al, 2023 ). ATP1.0-L sensor, an ATP sensor with lower affinity and faster kinetics, may be useful to detect local release of ATP ( Wu et al, 2022b ).…”

Section: Methods Of Measuring Extracellular Atp/adenosinementioning

confidence: 99%

“…Dopamine increases Ca 2+ signal events in astrocytes, suggesting a Ca 2+ -dependent mechanism underlies the ATP events. Hatashita et al examined spontaneous ATP dynamics in situ in the presence of TTX and in anesthetized mice using GRAB ATP1.0 ( Hatashita et al, 2023 ). The investigators found spatiotemporally diverse types of spontaneous ATP events.…”

Section: Extracellular Atp/adenosine Increases Induced By Neuronal Ac...mentioning

confidence: 99%

“…ATP elevations may occur locally, making measurements using enzyme-based biosensors on the surface of the brain tissue difficult. ATP release may occur locally in health ( Hatashita et al, 2023 ) and disease states ( Wu et al, 2022b ; Chen et al, 2022 ), and the rapid degradation of ATP ( Dunwiddie et al, 1997 ) may limit the spread of ATP into the extracellular milieu. Recently, our group found that, in an Alexander disease model, microglia display hyper-ramification and frequent Ca 2+ signals, both of which are mediated by P2Y 12 receptor activated by ATP presumably originate from astrocytes.…”

Section: Role Of Extracellular Atp/adenosine In Seizure Modelsmentioning

confidence: 99%

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Extracellular ATP/adenosine dynamics in the brain and its role in health and disease

Shigetomi,

Sakai,

Koizumi

2024

Front. Cell Dev. Biol.

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Extracellular ATP and adenosine are neuromodulators that regulate numerous neuronal functions in the brain. Neuronal activity and brain insults such as ischemic and traumatic injury upregulate these neuromodulators, which exert their effects by activating purinergic receptors. In addition, extracellular ATP/adenosine signaling plays a pivotal role in the pathogenesis of neurological diseases. Virtually every cell type in the brain contributes to the elevation of ATP/adenosine, and various mechanisms underlying this increase have been proposed. Extracellular adenosine is thought to be mainly produced via the degradation of extracellular ATP. However, adenosine is also released from neurons and glia in the brain. Therefore, the regulation of extracellular ATP/adenosine in physiological and pathophysiological conditions is likely far more complex than previously thought. To elucidate the complex mechanisms that regulate extracellular ATP/adenosine levels, accurate methods of assessing their spatiotemporal dynamics are needed. Several novel techniques for acquiring spatiotemporal information on extracellular ATP/adenosine, including fluorescent sensors, have been developed and have started to reveal the mechanisms underlying the release, uptake and degradation of ATP/adenosine. Here, we review methods for analyzing extracellular ATP/adenosine dynamics as well as the current state of knowledge on the spatiotemporal dynamics of ATP/adenosine in the brain. We focus on the mechanisms used by neurons and glia to cooperatively produce the activity-dependent increase in ATP/adenosine and its physiological and pathophysiological significance in the brain.

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“…Astrocytes tightly and dynamically interact with synapses having a critical role in synaptic information processing (Araque et al, 1999; Araque et al, 2014; Durkee & Alfonso, 2019; Guerra‐Gomes et al, 2018; Perea et al, 2009; Perea & Araque, 2005), ultimately playing a critical function in cognitive (Kofuji & Araque, 2021), anxiety (Cho et al, 2022) and depressive‐like behavior (Banasr & Duman, 2008). A key step in the interaction between astrocytes and neurons is the calcium (Ca 2+ )‐dependent release of gliotransmitters, such as glutamate (de Ceglia et al, 2023; Navarrete & Araque, 2008; Perea et al, 2016), ATP (Gordon et al, 2005; Hatashita et al, 2023; Xiong et al, 2018), GABA (Le Meur et al, 2012), and D‐serine (Abreu et al, 2023; Henneberger et al, 2010; Robin et al, 2018), which in turn is triggered by a wide variety of membrane receptors for neurotransmitters and neuromodulators, including glutamate (Skowrońska et al, 2019), ATP (Baraibar et al, 2023; Jacob et al, 2014), GABA (Jiménez‐Dinamarca et al, 2022; Le Meur et al, 2012), and endocannabinoids (eCBs) receptors, among others (Corkrum et al, 2020; Perea et al, 2009; Volterra & Meldolesi, 2005).…”

Section: Introductionmentioning

confidence: 99%

Adenosine receptors are the on‐and‐off switch of astrocytic cannabinoid type 1 (CB1) receptor effect upon synaptic plasticity in the medial prefrontal cortex

Gonçalves‐Ribeiro,

Savchak,

Costa‐Pinto

et al. 2024

Glia

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The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca2+ signaling occurs through CB1R‐A2AR or CB1R‐A1R heteromers that ultimately impact mPFC synaptic plasticity. CB1R‐mediated Ca2+ transients increased and decreased when A1R and A2AR were activated, respectively, unveiling adenosine receptors as modulators of astrocytic CB1R. CB1R activation leads to an enhancement of long‐term potentiation (LTP) in the mPFC, under the control of A1R but not of A2AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca2+ level elevations, CB1R activation decreases LTP, which is not modified by A1R or A2AR. The present work suggests that CB1R has a homeostatic role on mPFC LTP, under the control of A1R, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca2+ signaling.

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Spontaneous and multifaceted ATP release from astrocytes at the scale of hundreds of synapses

Cited by 5 publications

References 84 publications

Modulation of Cellular Levels of Adenosine Phosphates and Creatine Phosphate in Cultured Primary Astrocytes

Modulation of Cellular Levels of Adenosine Phosphates and Creatine Phosphate in Cultured Primary Astrocytes

Extracellular ATP/adenosine dynamics in the brain and its role in health and disease

Adenosine receptors are the on‐and‐off switch of astrocytic cannabinoid type 1 (CB1) receptor effect upon synaptic plasticity in the medial prefrontal cortex

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