Spontaneous and multifaceted ATP 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:10.1101/2022.12.05.519082

Cited by 2 publications

(2 citation statements)

References 82 publications

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“…The increased ATP levels lasted up to 6 h after injury and although the actual concentration of ATP was not reported, neuronal death was reduced by oxATP indicating that ATP release induced by SCI is sufficient to activate P2X7r. Hatashita et al (2023) used a genetically encoded ATP sensor to measure the ATP concentration around cortical astrocytes and found that spontaneous ATP release from astrocytes in vivo reaches the low micromolar range. Interestingly, ATP levels in the cerebrospinal 10.3389/fncel.2023.1288676 fluid reach micromolar concentrations for several days after SCI (Zhai et al, 2021).…”

Section: P2x7r and Scimentioning

confidence: 99%

P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord

Falco,

Fabbiani,

Maciel

et al. 2023

Front. Cell. Neurosci.

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The ependyma of the spinal cord is a latent stem cell niche that is reactivated by injury, generating new cells that migrate to the lesion site to limit the damage. The mechanisms by which ependymal cells are reactivated after injury remain poorly understood. ATP has been proposed to act as a diffusible “danger signal” to alert about damage and start repair. Indeed, spinal cord injury (SCI) generates an increase in extracellular ATP around the lesion epicenter that lasts for several hours and affects the functional outcome after the damage. The P2X7 receptor (P2X7r) has functional properties (e.g., low sensitivity for ATP, high permeability for Ca2+) that makes it a suitable candidate to act as a detector of tissue damage. Because ependymal cells express functional P2X7r that generate an inward current and regenerative Ca2+ waves, we hypothesize that the P2X7r has a main role in the mechanisms by which progenitor-like cells in the ependyma react to tissue damage. To test this possibility, we simulated the P2X7r activation that occurs after SCI by in vivo intraspinal injection of the selective agonist BzATP nearby the central canal. We found that BzATP rescued ependymal cells from quiescence by triggering a proliferative response similar to that generated by injury. In addition, P2X7r activation by BzATP induced a shift of ependymal cells to a glial fibrillary acidic protein (GFAP) phenotype similar to that induced by injury. However, P2X7r activation did not trigger the migration of ependyma-derived cells as occurs after tissue damage. Injection of BzATP induced the expression of connexin 26 (Cx26) in ependymal cells, an event needed for the proliferative reaction after injury. BzATP did not induce these changes in ependymal cells of P2X7–/– mice supporting a specific action on P2X7r. In vivo blockade of P2X7r with the potent antagonist AZ10606120 reduced significantly the injury-induced proliferation of ependymal cells. Our data indicate that P2X7r has a key role in the “awakening” of the ependymal stem cell niche after injury and suggest purinergic signaling is an interesting target to improve the contribution of endogenous progenitors to repair.

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Section: P2x7r and Scimentioning

confidence: 99%

P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord

Falco,

Fabbiani,

Maciel

et al. 2023

Front. Cell. Neurosci.

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“…These responses are often called Ca 2+ signals. During a Ca 2+ signal, astrocytes release neuroactive molecules, called gliotransmitters, like glutamate and ATP [7,17,18] that modulate neuronal and synaptic activities [7,8]. Astrocytes from different brain regions also show diversity in gene expression, morphology, and characteristics of the Ca 2+ signals triggered [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Diverse Calcium Signaling in Astrocytes: Insights from a Computational Model

Bezerra,

Roque

2024

Preprint

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Astrocytes are complex cells that influence a variety of brain functions and behaviors. They are active cells that show a sharp increase in intracellular Ca2+concentration in response to neurotransmitters (events called Ca2+signals). The main source of intracellular Ca2+is the stores in endoplasmic reticulum (ER), released by the activation of IP3 receptor channels on the ER membrane. As neurons, astrocytes from different brain regions show distinct Ca2+signals. In addition, astrocytes can also show different patterns of Ca2+responses. It is not yet clear how the diversity of astrocyte response emerge from the same mech-anisms. Here we present a two variable astrocyte compartmental model for the Ca2+and IP3 dynamics. We show that Ca2+signals with different characteristics can emerge from changing the parameters associated with the Ca2+and IP3 dynamics and the transmembrane current. We also show that global Ca2+signals are required for the model to trigger different patterns of Ca2+responses. The model present here can be used to simulate astrocytes from different brain regions and with distinct types of response.

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

Cited by 2 publications

References 82 publications

P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord

P2X7 receptor activation awakes a dormant stem cell niche in the adult spinal cord

Diverse Calcium Signaling in Astrocytes: Insights from a Computational Model

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