Age- and location-related changes in microglial function

Ritzel, Rodney M.; Patel, Anita R.; Pan, Sarah; Crapser, Joshua; Hammond, Matt; Jellison, Evan; McCullough, Louise D.

doi:10.1016/j.neurobiolaging.2015.02.016

Cited by 134Neuroinflammation and Neurodegeneration MechanismsMultiple Sclerosis Research StudiesGenetics, Aging, and Longevity in Model Organisms

Age- and location-related changes in microglial function

Ritzel, Rodney M., Patel, Anita R., Pan, Sarah, Crapser, Joshua, Hammond, Matt, Jellison, Evan, McCullough, Louise D.·2015·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2015.02.016

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Abstract

Inflammation in the central nervous system (CNS) is primarily regulated by microglia. No longer considered a homogenous population, microglia display a high degree of heterogeneity, immunological diversity and regional variability in function. Given their low rate of self-renewal, the microenvironment in which microglia reside may play an important role in microglial senescence. This study examines age-related changes in microglia in the brain and spinal cord. Using ex-vivo flow cytometry analyses, functional assays were performed to assess changes in microglial morphology, oxidative stress, cytokine production, and phagocytic activity with age in both the brain and spinal cord. The regional CNS environment had a significant effect on microglial activity with age. Blood-CNS barrier permeability was greater in the aging spinal cord compared with aging brain; this was associated with increased tissue cytokine levels. Aged microglia had deficits in phagocytosis at baseline and after stimulus-induced activation. The identification of age-specific, high scatter microglia together with the use of ex-vivo functional analyses provides the first functional characterization of senescent microglia. Age and regional-specificity of CNS disease should be taken into consideration when developing immune-modulatory treatments.

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Both inflammation and reduced microglial phagocytic capacity in AD can contribute to the decline in synaptic plasticity observed in this pathology.
“Both inflammation and reduced microglial phagocytic capacity in AD can contribute to the decline in synaptic plasticity observed in this pathology (Ritzel et al., 2015; Udeochu et al., 2016).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Ritzel et al., 2015
Microglia in naturally aged mice appear to have lower phagocytic activity compared to young mice.
“Additionally, microglia in naturally aged mice appear to have lower phagocytic activity compared to young mice [48].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [48]
Although p16 is often considered a more reliable marker of senescence, it can also be upregulated in non-senescent contexts.
“Although p16 is often considered a more reliable marker of senescence, it can also be upregulated in non-senescent contexts [18,48,72].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [48]

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Authors: Ritzel, R. M., Patel, A. R., Pan, S., Crapser, J., Hammond, M., Jellison, E., & McCullough, L. D.
Affiliations: UConn Health (US)
Corresponding author: McCullough, Louise D.
ORCID: Ritzel, Rodney M.
Patel, Anita R.
Crapser, Joshua
Jellison, Evan
McCullough, Louise D.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2015-06
Volume: 36
Issue: 6
Pages: 2153-2163
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2015.02.016
OpenAlex: W2034035726
Cited by: 134
References: 56
Citations by year: 2026: 2 · 2025: 11 · 2024: 9 · 2023: 5 · 2022: 17 · 2021: 17 · 2020: 14 · 2019: 12 · 2018: 19 · 2017: 16 · 2016: 10 · 2015: 2
FWCI: 8.36
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (R21 NS076293-01A1, F31 NS083244-01A1)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: microglia, microglial senescence, aging, regional heterogeneity, spinal cord, brain, phagocytosis, oxidative stress, cytokine production, microglial morphology, neuroinflammation
MeSH terms: Aging, Animals, Blood-Brain Barrier, Central Nervous System, Male, Mice, Inbred C57BL, Phagocytosis, Cytokines, Cellular Senescence, Microglia, Oxidative Stress, Cellular Microenvironment

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Age- and location-related changes in microglial function

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