Astrocytic STAT3 activation and chronic itch require IP3R1/TRPC-dependent Ca2+ signals in mice

Shiratori-Hayashi, Miho; Chiharu, Yamaguchi; Eguchi, Kazushi; Shiraishi, Yuto; Kohno, Keita; Mikoshiba, Katsuhiko; Inoue, Kazuhide; Nishida, Motohiro; Tsuda, Masayuki

doi:10.1016/j.jaci.2020.06.039

Cited by 37 publications

(43 citation statements)

References 67 publications

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“…IP 3 R1 immunoreactivity was recently detected in spinal dorsal horn astrocytes (Shiratori-Hayashi et al, 2020) and, albeit with low stringency, in isolated astrocytes from adult mice (Chai et al, 2017). Using a state of the art TurboID construct to biotinylate proteins in the immediate proximity of tripartite synapses, Takano et al (2020) report enrichment of IP 3 R1 protein in the peri-synaptic astrocytic compartment (Takano et al, 2020).…”

Section: Astrocyte Proteomementioning

confidence: 99%

“…This IP 3 R-mediated Ca 2+ signaling is considered to trigger the activity-dependent and selective release of chemical transmitters (gliotransmitters) such as glutamate, D-serine, and ATP, which have distinct influences over neuronal activity. Initially, IP 3 R subtype 2 (IP 3 R2) was the only recognized Ca 2+ channel in astrocytes; However, advanced Ca 2+ imaging techniques have since identified novel Ca 2+ sources, including mitochondria (Agarwal et al, 2017), transient receptor potential ankyrin 1 (Shigetomi et al, 2012(Shigetomi et al, , 2013b, L-type voltage gated Ca 2+ channels (Letellier et al, 2016), sodium/calcium exchanger (Kirischuk et al, 1997;Boddum et al, 2016;Rose et al, 2020), and transient receptor potential canonical (Shiratori-Hayashi et al, 2020) amongst others, thereby expanding the known Ca 2+ signaling toolkit of astrocytes. Doubtlessly additional Ca 2+ channels and sources will emerge in the future.…”

Section: Introductionmentioning

confidence: 99%

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Astrocytic IP3Rs: Beyond IP3R2

Sherwood

Arizono

Panatier

et al. 2021

Front. Cell. Neurosci.

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Astrocytes are sensitive to ongoing neuronal/network activities and, accordingly, regulate neuronal functions (synaptic transmission, synaptic plasticity, behavior, etc.) by the context-dependent release of several gliotransmitters (e.g., glutamate, glycine, D-serine, ATP). To sense diverse input, astrocytes express a plethora of G-protein coupled receptors, which couple, via Gi/o and Gq, to the intracellular Ca2+ release channel IP3-receptor (IP3R). Indeed, manipulating astrocytic IP3R-Ca2+ signaling is highly consequential at the network and behavioral level: Depleting IP3R subtype 2 (IP3R2) results in reduced GPCR-Ca2+ signaling and impaired synaptic plasticity; enhancing IP3R-Ca2+ signaling affects cognitive functions such as learning and memory, sleep, and mood. However, as a result of discrepancies in the literature, the role of GPCR-IP3R-Ca2+ signaling, especially under physiological conditions, remains inconclusive. One primary reason for this could be that IP3R2 has been used to represent all astrocytic IP3Rs, including IP3R1 and IP3R3. Indeed, IP3R1 and IP3R3 are unique Ca2+ channels in their own right; they have unique biophysical properties, often display distinct distribution, and are differentially regulated. As a result, they mediate different physiological roles to IP3R2. Thus, these additional channels promise to enrich the diversity of spatiotemporal Ca2+ dynamics and provide unique opportunities for integrating neuronal input and modulating astrocyte–neuron communication. The current review weighs evidence supporting the existence of multiple astrocytic-IP3R isoforms, summarizes distinct sub-type specific properties that shape spatiotemporal Ca2+ dynamics. We also discuss existing experimental tools and future refinements to better recapitulate the endogenous activities of each IP3R isoform.

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Section: Astrocyte Proteomementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Astrocytic IP3Rs: Beyond IP3R2

Sherwood

Arizono

Panatier

et al. 2021

Front. Cell. Neurosci.

Self Cite

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“…Transient ischemia can promote metabolic changes in astrocytes mediated by calcium ions ( Shiratori-Hayashi et al, 2020 ), as mitochondria are released to nerve cells to enhance their survival. It can also play a neuroprotective role through the regulation of glutamate ( Mahmoud et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…The effects of running are quite obvious in the nervous system, and in degenerative diseases of the nervous system such as Alzheimer disease (Valenzuela et al, 2020), Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington chorea (Rosenberg and Yang, 2007;Belviranlı and Okudan, 2018). Diseases caused by inflammation of the nervous system have obvious effects.…”

Section: Discussionmentioning

confidence: 99%

Running Promotes Transformation of Brain Astrocytes Into Neuroprotective Reactive Astrocytes and Synaptic Formation by Targeting Gpc6 Through the STAT3 Pathway

Chen

Gao

et al. 2021

Front. Physiol.

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Ischemic stroke is caused by cerebral ischemia upon the blockage of an artery, which results in a high disability rate. Little is known regarding the mechanism of astrocyte function in cerebral ischemia. We aimed to determine the effects of running on the transformation of astrocytes, and subsequent synapse formation. A study of middle cerebral artery occlusion (MCAO) after running in vivo showed that running can promote the transformation of astrocytes toward the neuroprotective phenotype. Our findings of oxygen-glucose deprived astrocytes in vitro after running revealed that these astrocytes transformed into the neuroprotective phenotype, and that the expression of STAT3 and Gpc6 was increased. We confirmed that mechanistically, running can target Gpc6 through the STAT3 pathway and then regulate the number of synapses. We concluded that running promotes synapse proliferation by polarizing astrocytes toward the neuroprotective phenotype and ultimately leads to nerve regeneration.

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“…However, it is not possible to rule out other Ca 2+ -sensitive mechanisms. Indeed, both VRAC activity [ 122 ] and d -serine release may be regulated by TRPC (transient receptor potential canonical)-mediated Ca 2+ influx [ 159 ]. As commonly used inhibitors block hemichannel and VRAC [ 160 , 161 ], their importance in the tonic release is unclear.…”

Section: Molecular Mechanisms Of Astrocyte Mediated Co-agonismmentioning

confidence: 99%

NMDARs, Coincidence Detectors of Astrocytic and Neuronal Activities

Sherwood

Oliet

Panatier

2021

IJMS

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Synaptic plasticity is an extensively studied cellular correlate of learning and memory in which NMDARs play a starring role. One of the most interesting features of NMDARs is their ability to act as a co-incident detector. It is unique amongst neurotransmitter receptors in this respect. Co-incident detection is possible because the opening of NMDARs requires membrane depolarisation and the binding of glutamate. Opening of NMDARs also requires a co-agonist. Although the dynamic regulation of glutamate and membrane depolarization have been well studied in coincident detection, the role of the co-agonist site is unexplored. It turns out that non-neuronal glial cells, astrocytes, regulate co-agonist availability, giving them the ability to influence synaptic plasticity. The unique morphology and spatial arrangement of astrocytes at the synaptic level affords them the capacity to sample and integrate information originating from unrelated synapses, regardless of any pre-synaptic and post-synaptic commonality. As astrocytes are classically considered slow responders, their influence at the synapse is widely recognized as modulatory. The aim herein is to reconsider the potential of astrocytes to participate directly in ongoing synaptic NMDAR activity and co-incident detection.

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Astrocytic STAT3 activation and chronic itch require IP3R1/TRPC-dependent Ca2+ signals in mice

Cited by 37 publications

References 67 publications

Astrocytic IP3Rs: Beyond IP3R2

Astrocytic IP3Rs: Beyond IP3R2

Running Promotes Transformation of Brain Astrocytes Into Neuroprotective Reactive Astrocytes and Synaptic Formation by Targeting Gpc6 Through the STAT3 Pathway

NMDARs, Coincidence Detectors of Astrocytic and Neuronal Activities

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