Probing the Complexities of Astrocyte Calcium Signaling

Shigetomi, Eiji; Patel, Sandip; Khakh, Baljit S.

doi:10.1016/j.tcb.2016.01.003

Cited by 235 publications

(214 citation statements)

References 111 publications

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“…A hallmark of astroglial physiology is the ability to respond to ATP or glutamate by evoking calcium waves to control synaptic and neural circuit formation and function2162566676869. We demonstrated herein that both BR1 and H9 astrocytes respond to 100 μM ATP influx with calcium waves.…”

Section: Discussionmentioning

confidence: 73%

Derivation of Functional Human Astrocytes from Cerebral Organoids

Dezonne

Sartore

Nascimento

et al. 2017

Sci Rep

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Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells. The cellular isolation of cerebral organoids yielded cells that were morphologically and functionally like astrocytes. Immunolabelling and proteomic assays revealed that human organoid-derived astrocytes express the main astrocytic molecular markers, including glutamate transporters, specific enzymes and cytoskeletal proteins. We found that organoid-derived astrocytes strongly supported neuronal survival and neurite outgrowth and responded to ATP through transient calcium wave elevations, which are hallmarks of astrocyte physiology. Additionally, these astrocytes presented similar functional pathways to those isolated from adult human cortex by surgical procedures. This is the first study to provide proteomic and functional analyses of astrocytes isolated from human cerebral organoids. The isolation of these astrocytes holds great potential for the investigation of developmental and evolutionary features of the human brain and provides a useful approach to drug screening and neurodegenerative disease modelling.

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Section: Discussionmentioning

confidence: 73%

Derivation of Functional Human Astrocytes from Cerebral Organoids

Dezonne

Sartore

Nascimento

et al. 2017

Sci Rep

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“…However, research in this area also yielded conflicting results and controversy as to the Ca 2+ dependence of gliotransmitter release, the identity of gliotransmitters and the astrocyte specificity of the manipulations used to study these pathways (Hamilton and Attwell, 2010; Nedergaard and Verkhratsky, 2012; Sloan and Barres, 2014). It is important to note that the Ca 2+ -transients that occur in astrocytes are of a much slower time scale than what occurs in neurons during neurotransmission (Shigetomi et al, 2016). Thus, both the nature and the function of astrocytic Ca 2+ -transients are likely to be distinct from that of neuronal Ca 2+ -signaling, which underlie fast synaptic transmission.…”

Section: Astrocytes Are Integral Components Of Synapsesmentioning

confidence: 99%

Cell Biology of Astrocyte-Synapse Interactions

Allen

Eroğlu

2017

Neuron

829

603

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Astrocytes, the most abundant glial cells in the mammalian brain, are critical regulators of brain development and physiology through dynamic and often bidirectional interactions with neuronal synapses. Despite the clear importance of astrocytes for the establishment and maintenance of proper synaptic connectivity, our understanding of their role in brain function is still in its infancy. We propose that this is at least in part due to large gaps in our knowledge of the cell biology of astrocytes and the mechanisms they use to interact with synapses. In this review, we summarize some of the seminal findings that yield important insight into the cellular and molecular basis of astrocyte-neuron communication, focusing on the role of astrocytes in the development and remodeling of synapses. Furthermore, we will pose some pressing questions that need to be addressed to advance our mechanistic understanding of the role of astrocytes in regulating synaptic development.

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“…In addition, astrocytes regulate synapse formation, removal and function, as well as regulate blood flow (Allen, 2014; Bazargani and Attwell, 2015). Astrocytes also respond with intracellular calcium elevations during distinct responses in vivo such as locomotion and startle (Shigetomi et al, 2016) and they are implicated in the regulation of complex mouse behaviours (Halassa and Haydon, 2010). …”

Section: Introductionmentioning

confidence: 99%

New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo

Srinivasan

Chai

et al. 2016

Neuron

Self Cite

359

387

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Summary Astrocytes exist throughout the nervous system and are proposed to affect neural circuits and behavior. However, studying astrocytes has proven difficult because of the lack of tools permitting astrocyte selective genetic manipulations. Here, we report the generation of Aldh1l1-Cre/ERT2 transgenic mice to selectively target astrocytes in vivo. We characterised Aldh1l1-Cre/ERT2 mice using imaging, immunohistochemistry, AAV-FLEX-GFP microinjections and crosses to RiboTag, Ai95 and new Cre-dependent membrane tethered Lck-GCaMP6f knock-in mice that we also generated. Two-to-three weeks after tamoxifen induction, Aldh1l1-Cre/ERT2 selectively targeted essentially all adult (P80) brain astrocytes with no detectable neuronal contamination, resulting in expression of cytosolic and Lck-GCaMP6f and permitting subcellular astrocyte calcium imaging during startle responses in vivo. Crosses with RiboTag mice allowed sequencing of actively translated mRNAs and determination of the adult cortical astrocyte transcriptome. Thus, we provide well characterised, easy-to-use resources with which to selectively study astrocytes in situ and in vivo in multiple experimental scenarios.

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Probing the Complexities of Astrocyte Calcium Signaling

Cited by 235 publications

References 111 publications

Derivation of Functional Human Astrocytes from Cerebral Organoids

Derivation of Functional Human Astrocytes from Cerebral Organoids

Cell Biology of Astrocyte-Synapse Interactions

New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo

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