Visualization of astrocytic intracellular Ca<sup>2+</sup> mobilization

Okubo, Yohei; Iino, Masamitsu

doi:10.1113/jp277609

Cited by 18 publications

(22 citation statements)

References 108 publications

(108 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although MAMs are enriched in ER-localized inositol triphosphate type 2 (IP3R2) receptors 55 , a previous study has shown that astrocytic mitochondrial Ca 2+ fluxes are independent of IP3R2 23 . An alternative possibility is that Ca 2+ transfer from the ER to mitochondria occurs through other isoforms of IP3 receptors, and ER-localized ryanodine receptors (RyRs) 56,57 . Thus, we surmise that spontaneous Ca 2+ events in astrocytic mitochondria occur at MAMs, and most likely involve Ca 2+ transfer to mitochondria via ER-localized isoforms of IP3 and RyR receptors.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic mitochondria in adult mouse brain slices show spontaneous calcium influx events with unique properties

Huntington¹,

Srinivasan²

2021

Cell Calcium

View full text Add to dashboard Cite

Astrocytes govern critical aspects of brain function via Ca 2+ signals, the majority of which associate with mitochondria. However, little is known with regard to in situ sources, kinetics or mechanisms of Ca 2+ influx in astrocytic mitochondria. To address this knowledge gap, we expressed the genetically encoded calcium indicator, GCaMP6f within the mitochondrial matrix of adult mouse astrocytes in the dorsolateral striatum (DLS) and hippocampus (HPC). We found spontaneous Ca 2+ events in astrocytic mitochondria with subcellular differences between somatic, branch, and branchlet mitochondria, as well as inter-regional differences between astrocytes in the DLS and HPC. We also found a strong dependency of spontaneous mitochondrial Ca 2+ fluxes on endoplasmic reticulum stores, the surprising lack of a major role for the mitochondrial calcium uniporter, MCU, and dual mitochondrial Ca 2+ responses with multiple neurotransmitter agonists. Together, our findings provide a foundational understanding of mechanisms for Ca 2+ influx in astrocytic mitochondria within disease-relevant brain regions.

show abstract

Section: Discussionmentioning

confidence: 99%

Astrocytic mitochondria in adult mouse brain slices show spontaneous calcium influx events with unique properties

Huntington¹,

Srinivasan²

2021

Cell Calcium

View full text Add to dashboard Cite

show abstract

“…Activation of GPCRs that stimulates phospholipase C-dependent production of InsP 3 serves as both a source of signaling and an enhancer of the integrative potential of astrocytic branches. In addition, Ca 2+ release from ER can be mediated by InsP 3 receptor-independent mechanisms, or Ca 2+ may be released from mitochondria in astrocytic branches [54,55]. In summary, there Box 2.…”

Section: Ionic Signaling In Branches and Leafletsmentioning

confidence: 99%

Astrocytic processes: from tripartite synapses to the active milieu

Semyanov

Verkhratsky

2021

Trends in Neurosciences

165

115

View full text Add to dashboard Cite

We define a new concept of 'active milieu' that unifies all components of nervous tissue (neuronal and glial compartments, extracellular space, extracellular matrix, and vasculature) into a dynamic information processing system. Within this framework, we focus on the role of astrocytic processes, classified into organellecontaining branches and organelle-free leaflets. We argue that astrocytic branches with emanating leaflets are homologous to dendritic shafts with spines. Within the active milieu, astrocytic processes are engaged in reciprocal interactions with neuronal compartments and communication with other cellular and non-cellular elements of the nervous tissue. The concept of the active milieuAxons of neurons provide the input and output of the central nervous system, whereas the intricate web of neurons, glia, and vasculature underlies information processing and defines the central nervous system function as an organ. The concept of tripartite synapse [1] has been instrumental in rethinking the role of astrocytes in synaptic transmission. Subsequent morphological analyses identified additional components of the synaptic structure. These components include microglial processes and the extracellular matrix (ECM), thus upgrading the tripartite paradigm to tetra-or pentapartite synapse [2,3]. These convolutions reflect a high degree of complexity of the perisynaptic microenvironment, a subject of remarkable morphological plasticity. In particular, interactions of synapses with their microenvironment are influenced by the interposition of individual synapses and nearby compartments of non-neuronal cells and extracellular space (ECS). Here we argue that the expanding knowledge on physiological interactions of cellular and non-cellular components of nervous tissue necessitates advancing the concept of 'tri-(multi)-partite synapse' to a concept we name 'active milieu'. The active milieu is based on the dynamic interposition and interaction among compartments of neurons, astrocytes, oligodendrocytes, microglia, blood vessels, ECS, and ECM (Box 1 and Figure 1). In the framework of this concept, neuronal activity not only propagates from one neuron to another but also signals to other cellular and noncellular elements, which respond to this signal and affect all components of nervous tissue.

show abstract

“…Thus, "artificial" induction of Ca 2+ rise in astroglial cells might mimic the activation achieved by ligands of GPCRs, K + , ATP, or cytokines. As a result of activation, extracellular K+ concentrations transiently rise, astrocytes release gliotransmitters and change their mitochondrial activity and proliferative status [172][173][174]. Actually, this is a principle of optogenetic photostimulation of astroglial cells expressing ChR2 or optoGPCRs under the astroglial promoters (i.e., GFAP), which recently appeared as a new approach to control brain activity [175][176][177][178].…”

Section: Optogenetic Targeting Of Gfap + Cells In the Neurogenic Niche: Established And Prospective Approaches To Cells Activation And Simentioning

confidence: 99%

Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

Салмина

Kapkaeva

Ветчинова

et al. 2021

IJMS

View full text Add to dashboard Cite

Neurogenesis is a key mechanism of brain development and plasticity, which is impaired in chronic neurodegeneration, including Parkinson’s disease. The accumulation of aberrant α-synuclein is one of the features of PD. Being secreted, this protein produces a prominent neurotoxic effect, alters synaptic plasticity, deregulates intercellular communication, and supports the development of neuroinflammation, thereby providing propagation of pathological events leading to the establishment of a PD-specific phenotype. Multidirectional and ambiguous effects of α-synuclein on adult neurogenesis suggest that impaired neurogenesis should be considered as a target for the prevention of cell loss and restoration of neurological functions. Thus, stimulation of endogenous neurogenesis or cell-replacement therapy with stem cell-derived differentiated neurons raises new hopes for the development of effective and safe technologies for treating PD neurodegeneration. Given the rapid development of optogenetics, it is not surprising that this method has already been repeatedly tested in manipulating neurogenesis in vivo and in vitro via targeting stem or progenitor cells. However, niche astrocytes could also serve as promising candidates for controlling neuronal differentiation and improving the functional integration of newly formed neurons within the brain tissue. In this review, we mainly focus on current approaches to assess neurogenesis and prospects in the application of optogenetic protocols to restore the neurogenesis in Parkinson’s disease.

show abstract

Visualization of astrocytic intracellular Ca²⁺ mobilization

Cited by 18 publications

References 108 publications

Astrocytic mitochondria in adult mouse brain slices show spontaneous calcium influx events with unique properties

Astrocytic mitochondria in adult mouse brain slices show spontaneous calcium influx events with unique properties

Astrocytic processes: from tripartite synapses to the active milieu

Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

Contact Info

Product

Resources

About

Visualization of astrocytic intracellular Ca2+ mobilization

Cited by 18 publications

References 108 publications

Astrocytic mitochondria in adult mouse brain slices show spontaneous calcium influx events with unique properties

Astrocytic mitochondria in adult mouse brain slices show spontaneous calcium influx events with unique properties

Astrocytic processes: from tripartite synapses to the active milieu

Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

Contact Info

Product

Resources

About

Visualization of astrocytic intracellular Ca²⁺ mobilization