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Cited by 387Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

Astrocyte Heterogeneity: Impact to Brain Aging and Disease

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Matias, Isadora, Morgado, Juliana, Gomes, Flávia Carvalho Alcantara·2019·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2019.00059PMC PMC6433753
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Abstract

Astrocytes, one of the largest glial cell population in the central nervous system (CNS), play a key function in several events of brain development and function, such as synapse formation and function, control of neurotransmitters release and uptake, production of trophic factors and control of neuronal survival. Initially described as a homogenous population, several evidences have pointed that astrocytes are highly heterogeneous, both morphologically and functionally, within the same region, and across different brain regions. Recent findings suggest that the heterogeneity in the expression profile of proteins involved in astrocyte function may predict the selective vulnerability of brain regions to specific diseases, as well as to the age-related cognitive decline. However, the molecular mechanisms underlying these changes, either in aging as well as in brain disease are scarce. Neuroinflammation, a hallmark of several neurodegenerative diseases and aging, is reported to have a dubious impact on glial activation, as these cells release pro- and anti-inflammatory cytokines and chemokines, anti-oxidants, free radicals, and neurotrophic factors. Despite the emerging evidences supporting that reactive astrocytes have a duality in their phenotype, neurotoxic or neuroprotective properties, depending on the age and stimuli, the underlying mechanisms of their activation, cellular interplays and the impact of regional astrocyte heterogeneity are still a matter of discussion. In this review article, we will summarize recent findings on astrocyte heterogeneity and phenotypes, as well as their likely impact for the brain function during aging and neural diseases. We will focus on the molecules and mechanisms triggered by astrocyte to control synapse formation in different brain regions. Finally, we will discuss new evidences on how the modulation of astrocyte phenotype and function could impact the synaptic deficits and glial dysfunction present in aging and pathological states.

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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 [49]

    The section on reactive astrocyte phenotypes (page unavailable) links reactivity to inflammatory responses and scar formation. The neurodegenerative-diseases section suggests that astrocyte atrophy may diminish synaptic coverage and impair the neurovascular unit, but does not establish those effects generally. The copy describes normal astrocytic control of glutamate and says BBB disruption affects the extent of reactivity; it does not establish glutamate dyshomeostasis or BBB breakdown as consequences of reactivity. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Matias, I., Morgado, J., & Gomes, F. C. A.
Affiliations
Universidade Federal do Rio de Janeiro (BR)
ORCID
Matias, Isadora
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2019-03-19
Volume
11
Pages
59-59
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2019.00059
PMC
PMC6433753
OpenAlex
W2920279714
Cited by
387
References
38
Citations by year
2026: 28 · 2025: 49 · 2024: 38 · 2023: 70 · 2022: 65 · 2021: 72 · 2020: 53 · 2019: 11
FWCI
5.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging 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
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Ministério da Saúde
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
astrocyte heterogeneity, astrocyte phenotype, brain aging, neuroinflammation, reactive astrocytes, synaptogenesis, age-related cognitive decline, neurodegenerative diseases, glial dysfunction, regional brain vulnerability, neuroprotection, cytokines and chemokines

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