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Cited by 131Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

Emerging Roles of Astrocytes in Neuro-Vascular Unit and the Tripartite Synapse With Emphasis on Reactive Gliosis in the Context of Alzheimer’s Disease

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Liu, Cai-Yun, Yang, Yu, Ju, Wei-Na, Wang, Xu, Zhang, Hong-Liang·2018·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2018.00193PMC PMC6048287
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Abstract

Astrocytes, which are five-fold more numerous than neurons in the central nervous system (CNS), are traditionally viewed to provide simple structural and nutritional supports for neurons and to participate in the composition of the blood brain barrier (BBB). In recent years, the active roles of astrocytes in regulating cerebral blood flow (CBF) and in maintaining the homeostasis of the tripartite synapse have attracted increasing attention. More importantly, astrocytes have been associated with the pathogenesis of Alzheimer's disease (AD), a major cause of dementia in the elderly. Although microglia-induced inflammation is considered important in the development and progression of AD, inflammation attributable to astrogliosis may also play crucial roles. A1 reactive astrocytes induced by inflammatory stimuli might be harmful by up-regulating several classical complement cascade genes thereby leading to chronic inflammation, while A2 induced by ischemia might be protective by up-regulating several neurotrophic factors. Here we provide a concise review of the emerging roles of astrocytes in the homeostasis maintenance of the neuro-vascular unit (NVU) and the tripartite synapse with emphasis on reactive astrogliosis in the context of AD, so as to pave the way for further research in this area, and to search for potential therapeutic targets of AD.

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  • 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 [48]

    The Astrogliosis section associates reactive astrocytes with inflammation and says severe astrogliosis can involve scar formation; it also discusses inflammatory mediators from activated astrocytes that may contribute to BBB deterioration. But the paper places reduced coverage of vessels and synapses and disrupted glutamate homeostasis under Astro-degeneration, not reactivity. It also describes normal astrogliosis as supporting glutamate uptake and BBB repair, so it does not support presenting the entire list as unfavorable consequences of reactivity. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Alterations in gliosis, especially astrocyte dysfunction, impact synaptic health.

    “Alterations in gliosis, especially astrocyte dysfunction, impacts synaptic health [36].”

    From Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways (2022) · cites this paper as [36]

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Cited by

Sorted by citations

Authors
Liu, C.-Y., Yang, Y., Ju, W.-N., Wang, X., & Zhang, H.-L.
Affiliations
First Hospital of Jilin University (CN)
Corresponding author
Wang, Xu
ORCID
Wang, Xu
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2018-07-10
Volume
12
Pages
193-193
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2018.00193
PMC
PMC6048287
OpenAlex
W2808172467
Cited by
131
References
33
Citations by year
2026: 10 · 2025: 12 · 2024: 15 · 2023: 20 · 2022: 22 · 2021: 19 · 2020: 19 · 2019: 10 · 2018: 2
FWCI
1.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (31600820, 81471216, 81500911)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
astrocytes, neurovascular unit, tripartite synapse, reactive astrogliosis, Alzheimer's disease, cerebral blood flow, blood-brain barrier, complement system, neuroinflammation, ischemia, neurotrophic factors, therapeutic target

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