Astrocytes in Migration

Zhan, Jiangshan; Gao, Kai; Chai, Rui; Jia, Xi Hua; Luo, Dao Peng; Guo, Gongde; Jiang, Yu Wu; Fung, Yin-Wan Wendy; Li, Lina; Yu, Albert Cheung Hoi

doi:10.1007/s11064-016-2089-4

Cited by 53 publications

(54 citation statements)

References 113 publications

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“…Cell migration can be classified using several criteria, for example, single cell vs collective migration (Rorth, 2009), ameboid versus integrin-dependant (Friedl & Brocker, 2000) or confined vs unrestricted migration (Hung et al, 2016). In the healthy adult brain, astrocytes do not generally migrate (Zhan et al, 2017). However, in neuroinflammatory states or following traumatic tissue injury, reactive astrocytes can change shape, become hypertrophic (Sofroniew & Vinters, 2010), contribute to glial scarring (Buffo, Rolando, & Ceruti, 2010) and display integrin-dependent migration (Cardenas, Kong, Alvarez, Maldonado, & Leyton, 2014).…”

Section: Astrocyte Migrationmentioning

confidence: 99%

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Velasco‐Estevez

Rolle

Mampay

et al. 2019

Glia

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Astrocytes are important for information processing in the brain and they achieve this by fine‐tuning neuronal communication via continuous uptake and release of biochemical modulators of neurotransmission and synaptic plasticity. Often overlooked are their important functions in mechanosensation. Indeed, astrocytes can detect pathophysiological changes in the mechanical properties of injured, ageing, or degenerating brain tissue. We have recently shown that astrocytes surrounding mechanically‐stiff amyloid plaques upregulate the mechanosensitive ion channel, Piezo1. Moreover, ageing transgenic Alzheimer's rats harboring a chronic peripheral bacterial infection displayed enhanced Piezo1 expression in amyloid plaque‐reactive astrocytes of the hippocampus and cerebral cortex. Here, we have shown that the bacterial endotoxin, lipopolysaccharide (LPS), also upregulates Piezo1 in primary mouse cortical astrocyte cultures in vitro. Activation of Piezo1, via the small molecule agonist Yoda1, enhanced Ca2+ influx in both control and LPS‐stimulated astrocytes. Moreover, Yoda1 augmented intracellular Ca2+ oscillations but decreased subsequent Ca2+ influx in response to adenosine triphosphate (ATP) stimulation. Neither blocking nor activating Piezo1 affected cell viability. However, LPS‐stimulated astrocyte cultures exposed to the Piezo1 activator, Yoda1, migrated significantly slower than reactive astrocytes treated with the mechanosensitive channel‐blocking peptide, GsMTx4. Furthermore, our data show that activating Piezo1 channels inhibits the release of cytokines and chemokines, such as IL‐1β, TNFα, and fractalkine (CX3CL1), from LPS‐stimulated astrocyte cultures. Taken together, our results suggest that astrocytic Piezo1 upregulation may act to dampen neuroinflammation and could be a useful drug target for neuroinflammatory disorders of the brain.

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Section: Astrocyte Migrationmentioning

confidence: 99%

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Velasco‐Estevez

Rolle

Mampay

et al. 2019

Glia

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“…As shown in vivo , astrocytes rather proliferate and grow towards a lesion than actively migrate into the injury site (Bardehle et al, ). However, after performing a scratch in a confluent astrocyte layer in vitro astrocytes recover the cell‐free area by proliferation, growth and migration (Zhan et al, ). The TRPC3‐induced Ca 2+ signals might translate into changes in proliferation, growth and migration of astrocytes.…”

Section: Resultsmentioning

confidence: 99%

TRPC1‐ and TRPC3‐dependent Ca²⁺ signaling in mouse cortical astrocytes affects injury‐evoked astrogliosis in vivo

Belkacemi¹,

Niermann²,

Hofmann³

et al. 2017

Glia

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Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+. Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3 and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co-expression of Trpc1 and Trpc3 in HEK-293 cells both proteins co-immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain-of-function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3−/− but increased in Trpc1−/− mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.

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“…Astrocytes in the adult brain are non-migratory cells; i.e., are quiescent under normal physiological conditions. However, they can be activated to become migratory under pathological conditions such as trauma, ischemia, infection, inflammation and neurodegeneration (Zhan, 2017). Recent in vivo studies indicate that reactive astrocytes undergo hypertrophy, cell polarization, and cell migration (Bardehle, 2013;Moore and Jessberger, 2013;Sirko, 2013).…”

Section: Connexins and Astrocyte Migrationmentioning

confidence: 99%

Connexins in Astrocyte Migration

et al. 2020

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Astrocytes have long been considered the supportive cells of the central nervous system, but during the last decades, they have gained much more attention because of their active participation in the modulation of neuronal function. For example, after brain damage, astrocytes become reactive and undergo characteristic morphological and molecular changes, such as hypertrophy and increase in the expression of glial fibrillary acidic protein (GFAP), in a process known as astrogliosis. After severe damage, astrocytes migrate to the lesion site and proliferate, which leads to the formation of a glial scar. At this scarforming stage, astrocytes secrete many factors, such as extracellular matrix proteins, cytokines, growth factors and chondroitin sulfate proteoglycans, stop migrating, and the process is irreversible. Although reactive gliosis is a normal physiological response that can protect brain cells from further damage, it also has detrimental effects on neuronal survival, by creating a hostile and non-permissive environment for axonal repair. The transformation of astrocytes from reactive to scar-forming astrocytes highlights migration as a relevant regulator of glial scar formation, and further emphasizes the importance of efficient communication between astrocytes in order to orchestrate cell migration. The coordination between astrocytes occurs mainly through Connexin (Cx) channels, in the form of direct cell-cell contact (gap junctions, GJs) or contact between the extracellular matrix and the astrocytes (hemichannels, HCs). Reactive astrocytes increase the expression levels of several proteins involved in astrocyte migration, such as a v b 3 Integrin, Syndecan-4 proteoglycan, the purinergic receptor P2X7, Pannexin1, and Cx43 HCs. Evidence has indicated that Cx43 HCs play a role in regulating astrocyte migration through the release of small molecules to the extracellular space, which then activate receptors in the same or adjacent cells to continue the signaling cascades required for astrocyte migration. In this review, we describe the communication of astrocytes through Cxs, the role of Cxs in inflammation and astrocyte migration, and discuss the molecular mechanisms that regulate Cx43 HCs, which may provide a therapeutic window of opportunity to control astrogliosis and the progression of neurodegenerative diseases.

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Astrocytes in Migration

Cited by 53 publications

References 113 publications

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

TRPC1‐ and TRPC3‐dependent Ca²⁺ signaling in mouse cortical astrocytes affects injury‐evoked astrogliosis in vivo

Connexins in Astrocyte Migration

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Astrocytes in Migration

Cited by 53 publications

References 113 publications

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

TRPC1‐ and TRPC3‐dependent Ca2+ signaling in mouse cortical astrocytes affects injury‐evoked astrogliosis in vivo

Connexins in Astrocyte Migration

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TRPC1‐ and TRPC3‐dependent Ca²⁺ signaling in mouse cortical astrocytes affects injury‐evoked astrogliosis in vivo