Astrocyte-immune cell interactions in physiology and pathology

Han, Rafael Taeho; Kim, Rachel D.; Molofsky, Anna V.; Liddelow, Shane A.

doi:10.1016/j.immuni.2021.01.013

Cited by 146 publications

(114 citation statements)

References 174 publications

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“…Mainly under the control of NFκB, the master regulator of inflammation, microglia, and astrocytes becomes an important source of several inflammatory mediators, including tumor necrosis factor alpha (TNF-α), interleukins (IL-1β, IL-6, IL-18), chemokines, and prostaglandins, in addition to nitric oxide (NO) and ROS [ 32 , 61 ]. This plethora of inflammatory mediators will impact the surrounding environment, importantly participating in the inflammatory activation of the other glial cells and in the recruitment of peripheral immune cells [ 32 , 62 ]. Excessive and chronic inflammatory responses lead to neuronal death and are involved in several CNS disorders [ 63 ].…”

Section: Neurochemical Changes and Molecular Mechanisms Associated With Gliotoxicitymentioning

confidence: 99%

Gliotoxicity and Glioprotection: the Dual Role of Glial Cells

et al. 2021

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Glial cells (astrocytes, oligodendrocytes and microglia) are critical for the central nervous system (CNS) in both physiological and pathological conditions. With this in mind, several studies have indicated that glial cells play key roles in the development and progression of CNS diseases. In this sense, gliotoxicity can be referred as the cellular, molecular, and neurochemical changes that can mediate toxic effects or ultimately lead to impairment of the ability of glial cells to protect neurons and/or other glial cells. On the other hand, glioprotection is associated with specific responses of glial cells, by which they can protect themselves as well as neurons, resulting in an overall improvement of the CNS functioning. In addition, gliotoxic events, including metabolic stresses, inflammation, excitotoxicity, and oxidative stress, as well as their related mechanisms, are strongly associated with the pathogenesis of neurological, psychiatric and infectious diseases. However, glioprotective molecules can prevent or improve these glial dysfunctions, representing glial cells-targeting therapies. Therefore, this review will provide a brief summary of types and functions of glial cells and point out cellular and molecular mechanisms associated with gliotoxicity and glioprotection, potential glioprotective molecules and their mechanisms, as well as gliotherapy. In summary, we expect to address the relevance of gliotoxicity and glioprotection in the CNS homeostasis and diseases.

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Section: Neurochemical Changes and Molecular Mechanisms Associated With Gliotoxicitymentioning

confidence: 99%

Gliotoxicity and Glioprotection: the Dual Role of Glial Cells

et al. 2021

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“…In the healthy CNS, astroglia provide structural support to neurons and separation from the parenchymal structures, including the meninges and blood vessels [ 49 ]. They play key roles in glucose metabolism, blood flow regulation, and synapse development and plasticity [ 50 ]. Astrocytes also maintain brain homeostasis by balancing ions, extracellular fluids, and neurotransmitters.…”

Section: The Innate Immune System Of the Brain And Atp Signalingmentioning

confidence: 99%

Pannexin-1 Channels as Mediators of Neuroinflammation

Seo

Dalal

Contreras

2021

IJMS

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Neuroinflammation is a major component of central nervous system (CNS) injuries and neurological diseases, including Alzheimer’s disease, multiple sclerosis, neuropathic pain, and brain trauma. The activation of innate immune cells at the damage site causes the release of pro-inflammatory cytokines and chemokines, which alter the functionality of nearby tissues and might mediate the recruitment of leukocytes to the injury site. If this process persists or is exacerbated, it prevents the adequate resolution of the inflammation, and ultimately enhances secondary damage. Adenosine 5′ triphosphate (ATP) is among the molecules released that trigger an inflammatory response, and it serves as a chemotactic and endogenous danger signal. Extracellular ATP activates multiple purinergic receptors (P2X and P2Y) that have been shown to promote neuroinflammation in a variety of CNS diseases. Recent studies have shown that Pannexin-1 (Panx1) channels are the principal conduits of ATP release from dying cells and innate immune cells in the brain. Herein, we review the emerging evidence that directly implicates Panx-1 channels in the neuroinflammatory response in the CNS.

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“…Given their complexity, a consensus statement about reactive astrocytes [123] recently recommended that astrocyte phenotypes should be defined by a combination of molecular markers and functional readouts. There is evidence that heterogeneity of astrocytes and microglial hallmarks expression can be bi-directionally controlled [124]. Although understanding how different glial subpopulations regulate their local niche under HFD-induced hypothalamic inflammation still need to be investigated.…”

Section: Hypothalamic Microglia-astrocyte Crosstalkmentioning

confidence: 99%

Hypothalamic Microglial Heterogeneity and Signature under High Fat Diet–Induced Inflammation

Mendes

Jara

Zanesco

et al. 2021

IJMS

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Under high-fat feeding, the hypothalamus atypically undergoes pro-inflammatory signaling activation. Recent data from transcriptomic analysis of microglia from rodents and humans has allowed the identification of several microglial subpopulations throughout the brain. Numerous studies have clarified the roles of these cells in hypothalamic inflammation, but how each microglial subset plays its functions upon inflammatory stimuli remains unexplored. Fortunately, these data unveiling microglial heterogeneity have triggered the development of novel experimental models for studying the roles and characteristics of each microglial subtype. In this review, we explore microglial heterogeneity in the hypothalamus and their crosstalk with astrocytes under high fat diet–induced inflammation. We present novel currently available ex vivo and in vivo experimental models that can be useful when designing a new research project in this field of study. Last, we examine the transcriptomic data already published to identify how the hypothalamic microglial signature changes upon short-term and prolonged high-fat feeding.

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Astrocyte-immune cell interactions in physiology and pathology

Cited by 146 publications

References 174 publications

Gliotoxicity and Glioprotection: the Dual Role of Glial Cells

Gliotoxicity and Glioprotection: the Dual Role of Glial Cells

Pannexin-1 Channels as Mediators of Neuroinflammation

Hypothalamic Microglial Heterogeneity and Signature under High Fat Diet–Induced Inflammation

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