Crosstalk Between Astrocytes and Microglia: An Overview

Matejuk, Agata; Ransohoff, Richard M.

doi:10.3389/fimmu.2020.01416

Cited by 293 publications

(212 citation statements)

References 91 publications

(119 reference statements)

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“…Astroglia form complex networks that are ubiquitously found in all brain regions, spinal cord, and all neuronal layers. They are connected by gap junctions and form long processes with end feet that communicate with blood vessels and also ensheathe synapses [ 201 ]. Astroglial networks are vast, and these cells organize communication pathways, structural architecture, and plasticity of the brain [ 231 ].…”

Section: Interactions Between Microglia and Astrogliamentioning

confidence: 99%

Interactions of neuroimmune signaling and glutamate plasticity in addiction

Gipson

Rawls

Scofield

et al. 2021

J Neuroinflammation

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Chronic use of drugs of abuse affects neuroimmune signaling; however, there are still many open questions regarding the interactions between neuroimmune mechanisms and substance use disorders (SUDs). Further, chronic use of drugs of abuse can induce glutamatergic changes in the brain, but the relationship between the glutamate system and neuroimmune signaling in addiction is not well understood. Therefore, the purpose of this review is to bring into focus the role of neuroimmune signaling and its interactions with the glutamate system following chronic drug use, and how this may guide pharmacotherapeutic treatment strategies for SUDs. In this review, we first describe neuroimmune mechanisms that may be linked to aberrant glutamate signaling in addiction. We focus specifically on the nuclear factor-kappa B (NF-κB) pathway, a potentially important neuroimmune mechanism that may be a key player in driving drug-seeking behavior. We highlight the importance of astroglial-microglial crosstalk, and how this interacts with known glutamatergic dysregulations in addiction. Then, we describe the importance of studying non-neuronal cells with unprecedented precision because understanding structure-function relationships in these cells is critical in understanding their role in addiction neurobiology. Here we propose a working model of neuroimmune-glutamate interactions that underlie drug use motivation, which we argue may aid strategies for small molecule drug development to treat substance use disorders. Together, the synthesis of this review shows that interactions between glutamate and neuroimmune signaling may play an important and understudied role in addiction processes and may be critical in developing more efficacious pharmacotherapies to treat SUDs.

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Section: Interactions Between Microglia and Astrogliamentioning

confidence: 99%

Interactions of neuroimmune signaling and glutamate plasticity in addiction

Gipson

Rawls

Scofield

et al. 2021

J Neuroinflammation

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“…In response to the neuronal deterioration of AD, the feedback mechanism of cortical cells to restore the damage initiates morphological and functional changes of neurons, even reprogramming neuronal proliferation [ 73 ]. At the early stage, glia undergo significant modifications in favor of neurons, contrary to the later stage when they become overstimulated and harmful to neurons in hyperinflammatory reactions.…”

Section: Paradoxical Functions Of Astrocytes In Alzheimer Diseasementioning

confidence: 99%

Deleterious Alteration of Glia in the Brain of Alzheimer’s Disease

Kim

Otgontenger

Jamsranjav

et al. 2020

IJMS

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The deterioration of neurons in Alzheimer’s disease (AD) arises from genetic, immunologic, and cellular factors inside the cortex. The traditional consensus of the amyloid-beta (Aβ) paradigm as a singular cause of AD has been under revision, with the accumulation of exploding neurobiological evidence. Among the multifaceted casualties of AD, the involvement of glia gains significance for its dynamic contribution to neurons, either in a neuroprotective or neurotoxic fashion. Basically, microglia and astrocytes contribute to neuronal sustainability by releasing neuroprotective cytokines, maintaining an adequate amount of glutamate in the synapse, and pruning excessive synaptic terminals. Such beneficial effects divert to the other detrimental cascade in chronic neuroinflammatory conditions. In this change, there are new discoveries of specific cytokines, microRNAs, and complementary factors. Previously unknown mechanisms of ion channels such as Kv1.3, Kir2.1, and HCN are also elucidated in the activation of microglia. The activation of glia is responsible for the excitotoxicity through the overflow of glutamate transmitter via mGluRs expressed on the membrane, which can lead to synaptic malfunction and engulfment. The communication between microglia and astrocytes is mediated through exosomes as well as cytokines, where numerous pieces of genetic information are transferred in the form of microRNAs. The new findings tell us that the neuronal environment in the AD condition is a far more complicated and dynamically interacting space. The identification of each molecule in the milieu and cellular communication would contribute to a better understanding of AD in the neurobiological perspective, consequently suggesting a possible therapeutic clue.

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“…The neurons, microglia, astrocytes, and oligodendrocytic lineage cells have been shown to interact with another, structurally and functionally, and they communicate with the peripheral leukocytes infiltrating the CNS or transiting via the perivascular space and other CNS borders (Neuroimmune Communication, 2017 ; Tay et al, 2017c ; Carrier et al, 2020 ). Microglia can control astrocytic functions, and vice versa, astrocytes can influence microglia, and the same holds for the reciprocal crosstalks taking place between astrocytes, microglia, and oligodendrocytic lineage cells (Béchade et al, 2013 ; Kettenmann et al, 2013 ; Domingues et al, 2016 ; Liddelow et al, 2017 ; Matejuk and Ransohoff, 2020 ). Within this integrative viewpoint, collaborative research endeavors that bridge complementary expertise with the different non-neuronal cell types, subtypes and phenotypes, are now required to provide maximal insights into the functional relevance of these multidimensional relationships within the CNS.…”

Section: The Challenge Of Studying Their Complex Relationshipsmentioning

confidence: 99%

A Diversity of Cell Types, Subtypes and Phenotypes in the Central Nervous System: The Importance of Studying Their Complex Relationships

Tremblay

2020

Front. Cell. Neurosci.

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Crosstalk Between Astrocytes and Microglia: An Overview

Cited by 293 publications

References 91 publications

Interactions of neuroimmune signaling and glutamate plasticity in addiction

Interactions of neuroimmune signaling and glutamate plasticity in addiction

Deleterious Alteration of Glia in the Brain of Alzheimer’s Disease

A Diversity of Cell Types, Subtypes and Phenotypes in the Central Nervous System: The Importance of Studying Their Complex Relationships

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