Microglia-Astrocyte Crosstalk: An Intimate Molecular Conversation
Abstract
Microglia-astrocyte crosstalk has recently been at the forefront of glial research. Emerging evidence illustrates that microglia- and astrocyte-derived signals are the functional determinants for the fates of astrocytes and microglia, respectively. By releasing diverse signaling molecules, both microglia and astrocytes establish autocrine feedback and their bidirectional conversation for a tight reciprocal modulation during central nervous system (CNS) insult or injury. Microglia, the constant sensors of changes in the CNS microenvironment and restorers of tissue homeostasis, not only serve as the primary immune cells of the CNS but also regulate the innate immune functions of astrocytes. Similarly, microglia determine the functions of reactive astrocytes, ranging from neuroprotective to neurotoxic. Conversely, astrocytes through their secreted molecules regulate microglial phenotypes and functions ranging from motility to phagocytosis. Altogether, the microglia-astrocyte crosstalk is fundamental to neuronal functions and dysfunctions. This review discusses the current understanding of the intimate molecular conversation between microglia and astrocytes and outlines its potential implications in CNS health and disease.
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Astrocytes can trigger microglia activation and regulate their cellular functions through the release of cytokines, chemokines, and growth factors.
“astrocytes can trigger microglia activation and regulate their cellular functions through the release of cytokines, chemokines, and growth factors [39].”
From Pharmacological ablation of astrocytes reduces Aβ degradation and synaptic connectivity in an ex vivo model of Alzheimer’s disease (2021) · cites this paper as [39]
Astrocyte reactivity has frequently been associated with neuroinflammation, unfavorable glial scar formation, glutamate dyshomeostasis, altered coverage of synapses and blood vessels, and BBB breakout.
“Hence, astrocyte reactivity has frequently been associated with neuroinflammation, unfavorable glial scar formation [7, 8, 9, 37, 38, 43, 48, 49], glutamate dyshomeostasis [43, 50, 51], altered coverage of synapses and blood vessels, and BBB breakout [38, 42, 43, 45, 46, 47].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [37]
Together with microglia, astrocytes constitute the principal defensive system of the CNS and respond to damage-related stimuli including Aβ and glutamate overload in a process known as astrocyte reactivity.
“Together with microglia, astrocytes constitute the principal defensive system of the CNS [37], responding to numerous damage‐related stimuli [6, 7, 8, 9] including amyloid β peptides (Aβ) and glutamate overload, in a process known as astrocyte reactivity [15, 37, 38, 39, 40].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [37]
Hyperactivated astrocytes and microglia support excitotoxicity through the exacerbated release of glutamate in response to Aβ, and GABA‐producing astrocytes are commonly found in AD.
“hyperactivated astrocytes and microglia, support excitotoxicity through the exacerbated release of glutamate in response to Aβ [37, 38, 40, 43, 50, 51, 117, 118], and even GABA‐producing astrocytes are commonly found in AD [42, 97, 119].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [37]
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- Authors
- Jha, M. K., Jo, M., Kim, J.-H., & Suk, K.
- Affiliations
- Johns Hopkins University (US)
- Kyungpook National University (KR)
- Corresponding author
- Suk, Kyoungho
- Venue
- The Neuroscientist
- Publisher
- SAGE Publications
- Published
- 2018-06-22
- Volume
- 25
- Issue
- 3
- Pages
- 227-240
- ISSN
- 1073-8584 (ISSN-L)
- 1089-4098
- OpenAlex
- W2808916408
- Cited by
- 579
- References
- 16
- Citations by year
- 2026: 40 · 2025: 80 · 2024: 73 · 2023: 111 · 2022: 94 · 2021: 90 · 2020: 67 · 2019: 22 · 2018: 1
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Neuroscientist (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea (NRF) funded by the Korean government (2015R1A2A1A10051958, 2016M3C7A1904148, NRF-2017R1A5A2015391)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- microglia, astrocytes, glial communication, reactive astrocytes, microglial phagocytosis, microglial motility, neuroinflammation, central nervous system injury, neuroprotection, neurotoxicity, autocrine signaling, innate immunity
- MeSH terms
- Animals, Astrocytes, Brain, Cell Communication, Cell Movement, Encephalitis, Humans, Immunity, Innate, Synaptic Transmission, Neurons, Phagocytosis, Microglia
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