Brain circuitry outside the synaptic cleft

Rusakov, Dmitri A.; Dityatev, Alexander

doi:10.1098/rstb.2013.0591

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…Through numerous processes specific to astrocyte morphology, they form close interactions with neurons and other glial cells [5]. Astrocytes are an indispensable part of synaptic transmission, as proposed by tripartite as well as tetraand pentapartite synapse models [6,7]. As suggested by Semyanov and Verkhratsky [8], astrocytes, microglia, oligodendrocytes, blood vessels, extracellular space, and the extracellular matrix form an active milleu where neuronal activity not only propagates among preand postsynaptic neurons, but also provides signals to the other cellular and noncellular compartments which affect the nervous tissue [8].…”

Section: Introductionmentioning

confidence: 99%

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Lazic

Balint

Ninković

et al. 2022

IJMS

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Astrocytes, as the most abundant glial cells in the central nervous system, are tightly integrated into neural networks and participate in numerous aspects of brain physiology and pathology. They are the main homeostatic cells in the central nervous system, and the loss of astrocyte physiological functions and/or gain of pro-inflammatory functions, due to their reactivation or cellular senescence, can have profound impacts on the surrounding microenvironment with pathological outcomes. Although the importance of astrocytes is generally recognized, and both senescence and reactive astrogliosis have been extensively reviewed independently, there are only a few comparative overviews of these complex processes. In this review, we summarize the latest data regarding astrocyte reactivation and senescence, and outline similarities and differences between these phenotypes from morphological, functional, and molecular points of view. A special focus has been given to neurodegenerative diseases, where these phenotypic alternations of astrocytes are significantly implicated. We also summarize current perspectives regarding new advances in model systems based on astrocytes as well as data pointing to these glial cells as potential therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Lazic

Balint

Ninković

et al. 2022

IJMS

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“…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.…”

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confidence: 99%

Astrocytic processes: from tripartite synapses to the active milieu

Semyanov

Verkhratsky

2021

Trends in Neurosciences

153

115

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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.

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“…The very close location of glial cells to synaptic regions and to ensheath synaptic clefts (Araque et al, 1999; Rusakov and Dityatev, 2014) facilitates their ability to regulate extracellular [K + ] around neurons by potassium spatial buffering (Orkand et al, 1966) and potassium siphoning (Newman et al, 1984). Elevation of extracellular K + shifts E K towards potentials more positive than resting, thereby favoring K + influx through Kir4.1 potassium channels under normal conditions (Neusch et al, 2006; Kucheryavykh et al, 2007; Olsen et al, 2007; Seifert et al, 2009; Olsen et al, 2015) and through members of the tandem pore family of K + channels (such as TREK channels) particularly during conditions of stress (such as during ischemia) (Kucheryavykh et al, 2009; Rivera-Pagán et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

A-Kinase-Anchoring Protein (AKAP150) is expressed in Astrocytes and Upregulated in Response to Ischemia

et al. 2018

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A-kinase-anchoring proteins, AKAPs, are scaffolding proteins that associate with kinases and phosphatases, and direct them to a specific submembrane site to coordinate signaling events. AKAP150, a rodent ortholog of human AKAP79, has been extensively studied in neurons, but very little is known about the localization and function of AKAP150 in astrocytes, the major cell type in brain. Thus, in this study, we assessed the localization of AKAP150 in astrocytes and elucidated its role during physiological and ischemic conditions. Herein, we demonstrate that AKAP150 is localized in astrocytes and is up-regulated during ischemia both in vitro and in vivo. Knock-down of AKAP150 by RNAi depolarizes the astrocytic membrane potential and substantially reduces by 80% the ability of astrocytes to take up extracellular potassium during ischemic conditions. Therefore, upregulation of AKAP150 during ischemia preserves potassium conductance and the associated hyperpolarized membrane potential of astrocytes; properties of astrocytes needed to maintain extracellular brain homeostasis. Taken together, these data suggest that AKAP150 may play a pivotal role in the neuroprotective mechanism of astrocytes during pathological conditions.

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Brain circuitry outside the synaptic cleft

Cited by 7 publications

References 22 publications

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Reactive and Senescent Astroglial Phenotypes as Hallmarks of Brain Pathologies

Astrocytic processes: from tripartite synapses to the active milieu

A-Kinase-Anchoring Protein (AKAP150) is expressed in Astrocytes and Upregulated in Response to Ischemia

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