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Cited by 251Neuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and TreatmentsNeuroscience and Neuropharmacology Research

The Neuron-Astrocyte-Microglia Triad in Normal Brain Ageing and in a Model of Neuroinflammation in the Rat Hippocampus

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Cerbai, Francesca, Lana, Daniele, Nosi, Daniele, Petkova-Kirova, Polina, Zecchi, Sandra, Brothers, Holly M., Wenk, Gary L., Giovannini, Maria Grazia·2012·PLoS ONE
DOI 10.1371/journal.pone.0045250PMC PMC3445467
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Abstract

Ageing is accompanied by a decline in cognitive functions; along with a variety of neurobiological changes. The association between inflammation and ageing is based on complex molecular and cellular changes that we are only just beginning to understand. The hippocampus is one of the structures more closely related to electrophysiological, structural and morphological changes during ageing. In the present study we examined the effect of normal ageing and LPS-induced inflammation on astroglia-neuron interaction in the rat hippocampus of adult, normal aged and LPS-treated adult rats. Astrocytes were smaller, with thicker and shorter branches and less numerous in CA1 Str. radiatum of aged rats in comparison to adult and LPS-treated rats. Astrocyte branches infiltrated apoptotic neurons of aged and LPS-treated rats. Cellular debris, which were more numerous in CA1 of aged and LPS-treated rats, could be found apposed to astrocytes processes and were phagocytated by reactive microglia. Reactive microglia were present in the CA1 Str. Radiatum, often in association with apoptotic cells. Significant differences were found in the fraction of reactive microglia which was 40% of total in adult, 33% in aged and 50% in LPS-treated rats. Fractalkine (CX3CL1) increased significantly in hippocampus homogenates of aged and LPS-treated rats. The number of CA1 neurons decreased in aged rats. In the hippocampus of aged and LPS-treated rats astrocytes and microglia may help clearing apoptotic cellular debris possibly through CX3CL1 signalling. Our results indicate that astrocytes and microglia in the hippocampus of aged and LPS-infused rats possibly participate in the clearance of cellular debris associated with programmed cell death. The actions of astrocytes may represent either protective mechanisms to control inflammatory processes and the spread of further cellular damage to neighboring tissue, or they may contribute to neuronal damage in pathological conditions.

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  • Studies in rodents document region-dependent and often contradictory changes in aging astrocytes, such as an increase in cellular volume and overlap of astrocyte processes, but also atrophy, increase in GFAP content, or even a reduction in the number of GFAP+ and GS+ astrocytes.

    “Studies in rodents document region-dependent and often contradictory changes in aging astrocytes, such as an increase in cellular volume and overlap of astrocyte processes, but also atrophy, increase in GFAP content, or even a reduction in the number of GFAP+ and GS+ astrocytes87–89.”

    From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [88]

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Authors
Cerbai, F., Lana, D., Nosi, D., Petkova-Kirova, P., Zecchi, S., Brothers, H. M., Wenk, G. L., & Giovannini, M. G.
Affiliations
  • University of Florence (IT)
  • Bulgarian Academy of Sciences (BG)
  • The Ohio State University (US)
Corresponding author
Giovannini, Maria Grazia
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-09-18
Volume
7
Issue
9
Pages
e45250
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0045250
PMC
PMC3445467
OpenAlex
W2063891183
Cited by
251
References
15
Citations by year
2026: 8 · 2025: 14 · 2024: 18 · 2023: 15 · 2022: 28 · 2021: 26 · 2020: 21 · 2019: 20 · 2018: 17 · 2017: 19 · 2016: 14 · 2015: 15 · 2014: 23 · 2013: 13
FWCI
8.22
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • U.S. Public Health Service (RO1 AG030331)
  • National Institute on Aging (R01AG037320, R01AG030331)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
brain aging, neuroinflammation, hippocampus, astrocytes, microglia, neuron-glia interactions, lipopolysaccharide, reactive microglia, astrocyte morphology, neuronal apoptosis, phagocytosis, fractalkine, CA1 stratum radiatum, cognitive decline
MeSH terms
Aging, Animals, Astrocytes, Disease Models, Animal, Hippocampus, Immunohistochemistry, Inflammation, Lipopolysaccharides, Male, Neurons, Phagocytosis, Signal Transduction, Rats, Wistar, Apoptosis, Microglia, Microscopy, Confocal, Rats, Chemokine CX3CL1

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