GABAergic‐astrocyte signaling: A refinement of inhibitory brain networks

Mederos, Sara; Perea, Gertrudis

doi:10.1002/glia.23644

Cited by 85 publications

(72 citation statements)

References 124 publications

(212 reference statements)

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“…We observed that the higher the serum GFAP concentration, the greater was the impairment in LICI, which is considered to reflect short-lasting postsynaptic inhibition mediated through the GABAB receptors at the level of local interneurons (Rossini et al, 2015;Ziemann et al, 2015). This is in line with the existence of dynamic GABAergic-astrocyte communication, GFAP being a major component of the astrocytic cytoskeleton (Mederos and Perea, 2019;Robel and Sontheimer, 2016).…”

Section: Discussionmentioning

confidence: 54%

Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

Benussi

Ashton

Karikari

et al. 2020

JAD

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Background: It is still unknown if serum glial fibrillary acidic protein (GFAP) is a useful marker in frontotemporal lobar degeneration (FTLD). Objective: To assess the diagnostic and prognostic value of serum GFAP in a large cohort of patients with FTLD. Methods: In this retrospective study, performed on 406 participants, we measured serum GFAP concentration with an ultrasensitive Single molecule array (Simoa) method in patients with FTLD, Alzheimer’s disease (AD), and in cognitively unimpaired elderly controls. We assessed the role of GFAP as marker of disease severity by analyzing the correlation with clinical variables, neurophysiological data, and cross-sectional brain imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease survival. Results: We observed significantly higher levels of serum GFAP in patients with FTLD syndromes, except progressive supranuclear palsy, compared with healthy controls, but not compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. Serum GFAP concentration was not a significant predictor of survival. Conclusion: Serum GFAP is increased in FTLD, correlates with cognition and GABAergic deficits, and thus shows promise as a biomarker of disease severity in FTLD.

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Section: Discussionmentioning

confidence: 54%

Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

Benussi

Ashton

Karikari

et al. 2020

JAD

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“…Astrocytes provide energy and metabolic substrates to support neuronal activity ( Brown and Ransom, 2007 , Nortley and Attwell, 2017 , Rouach et al, 2008 ). They maintain molecular homeostasis ( Marina et al, 2018 , Verkhratsky and Nedergaard, 2018 ), modulate neuronal excitability ( Halassa et al, 2007 , Mederos and Perea, 2019 , Montana et al, 2004 , Parpura et al, 1994 , Verkhratsky et al, 2020 ) and synaptic development, transmission, and plasticity ( Allen & Eroglu, 2017 ). Another important function of astrocytes is the maintenance of the blood-brain barrier (BBB).…”

Section: Introductionmentioning

confidence: 99%

Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

Acıoğlu

Heary

et al. 2021

Brain, Behavior, and Immunity

159

132

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Highlights Astroglial TLRs mediate host-defense and pathogen dissemination in CNS infections. Astroglial TLRs help clearance of protein aggregates in neurodegenerative diseases. Astroglial TLR signaling contributes to inflammation in CNS injury and disease. Signaling through TLRs promotes beneficial and detrimental functions of astrocytes. TLRs in astrocytes could be therapeutic targets in CNS disease and injury.

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“…Indeed, astroglial Ca 2+ oscillations driven by extracellular inputs superimpose on and integrate intrinsic Ca 2+ activity, thus making astrocytes active partners of network functioning. With some notable exceptions (Jennings et al, 2017;Xin et al, 2019), activation of G-protein coupled receptors (GPCRs) leads to intracellular Ca 2+ elevations (Kofuji and Araque, 2020) not only upon stimulation with molecules commonly considered excitatory, such as glutamate, but also with the canonical inhibitory neurotransmitter GABA (Perea et al, 2016;Mariotti et al, 2018;Mederos and Perea, 2019;Nagai et al, 2019). In line with these observations and contrary to their neuronal counterpart (Huang and Thathiah, 2015), in vivo chemogenetic activation of both G q and G i/o DREADDs elicited Ca 2+ increases in astrocytes , thus challenging the longestablished concept of E/I as mutually interplaying and yet still discernable processes (Isaacson and Scanziani, 2011).…”

Section: Astroglial Ca 2+ Dynamics At the Interface Of Glutamatergic mentioning

confidence: 99%

“…Especially in glutamatergic and purinergic transmission, the stimulus nature can be switched if presynaptic rather than postsynaptic receptors are activated (Serrano et al, 2006;Andersson et al, 2007;Hulme et al, 2014;Cavaccini et al, 2020). The connectivity of local circuits plays a major role when inhibitory transmission is potentiated by an excitatory transmitter (Kang et al, 1998;Crosby et al, 2018;Mederos and Perea, 2019), inhibitory transmission is inhibited, or excitatory transmission is disinhibited (Liu et al, 2004;Yarishkin et al, 2015). Associated to specific local circuits, distinct astroglial subpopulations (Zhang and Barres, 2010;Liddelow et al, 2017;Morel et al, 2017) interact with designated neuronal subtypes or circuits such as the striatal dopaminergic D1/D2 pathways (Martín et al, 2015;Martin-Fernandez et al, 2017).…”

Section: Astroglial Ca 2+ Bottleneck: Upstream and Downstream Signal mentioning

confidence: 99%

The Paradox of Astroglial Ca2 + Signals at the Interface of Excitation and Inhibition

Caudal

Gobbo

Scheller

et al. 2020

Front. Cell. Neurosci.

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Astroglial networks constitute a non-neuronal communication system in the brain and are acknowledged modulators of synaptic plasticity. A sophisticated set of transmitter receptors in combination with distinct secretion mechanisms enables astrocytes to sense and modulate synaptic transmission. This integrative function evolved around intracellular Ca2+ signals, by and large considered as the main indicator of astrocyte activity. Regular brain physiology meticulously relies on the constant reciprocity of excitation and inhibition (E/I). Astrocytes are metabolically, physically, and functionally associated to the E/I convergence. Metabolically, astrocytes provide glutamine, the precursor of both major neurotransmitters governing E/I in the central nervous system (CNS): glutamate and γ-aminobutyric acid (GABA). Perisynaptic astroglial processes are structurally and functionally associated with the respective circuits throughout the CNS. Astonishingly, in astrocytes, glutamatergic as well as GABAergic inputs elicit similar rises in intracellular Ca2+ that in turn can trigger the release of glutamate and GABA as well. Paradoxically, as gliotransmitters, these two molecules can thus strengthen, weaken or even reverse the input signal. Therefore, the net impact on neuronal network function is often convoluted and cannot be simply predicted by the nature of the stimulus itself. In this review, we highlight the ambiguity of astrocytes on discriminating and affecting synaptic activity in physiological and pathological state. Indeed, aberrant astroglial Ca2+ signaling is a key aspect of pathological conditions exhibiting compromised network excitability, such as epilepsy. Here, we gather recent evidence on the complexity of astroglial Ca2+ signals in health and disease, challenging the traditional, neuro-centric concept of segregating E/I, in favor of a non-binary, mutually dependent perspective on glutamatergic and GABAergic transmission.

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GABAergic‐astrocyte signaling: A refinement of inhibitory brain networks

Cited by 85 publications

References 124 publications

Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

The Paradox of Astroglial Ca2 + Signals at the Interface of Excitation and Inhibition

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