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Microglia undergo disease-associated transcriptional activation and CX3C motif chemokine receptor 1 expression regulates neurogenesis in the aged brain

Fritze, Jonas LU ; Muralidharan, Chandramouli LU orcid ; Stamp, Eleanor and Ahlenius, Henrik LU (2024) In Developmental Neurobiology 84(3). p.128-141
Abstract

Adult neurogenesis continues throughout life but declines dramatically with age and in neurodegenerative disorders such as Alzheimer's disease. In parallel, microglia become activated resulting in chronic inflammation in the aged brain. A unique type of microglia, suggested to support neurogenesis, exists in the subventricular zone (SVZ), but little is known how they are affected by aging. We analyzed the transcriptome of aging microglia and identified a unique neuroprotective activation profile in aged SVZ microglia, which is partly shared with disease-associated microglia (DAM). CX3C motif chemokine receptor 1 (CX3CR1) is characteristically expressed by brain microglia where it directs migration to targets for phagocytosis. We show... (More)

Adult neurogenesis continues throughout life but declines dramatically with age and in neurodegenerative disorders such as Alzheimer's disease. In parallel, microglia become activated resulting in chronic inflammation in the aged brain. A unique type of microglia, suggested to support neurogenesis, exists in the subventricular zone (SVZ), but little is known how they are affected by aging. We analyzed the transcriptome of aging microglia and identified a unique neuroprotective activation profile in aged SVZ microglia, which is partly shared with disease-associated microglia (DAM). CX3C motif chemokine receptor 1 (CX3CR1) is characteristically expressed by brain microglia where it directs migration to targets for phagocytosis. We show that Cx3cr1 expression, as in DAM, is downregulated in old SVZ microglia and that heterozygous Cx3cr1 mice have increased proliferation and neuroblast number in the aged SVZ but not in the dentate gyrus, identifying CX3CR1 signaling as a novel age and brain region-specific regulator of neurogenesis.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aging, CX3C motif chemokine receptor 1, disease-associated microglia, microglia, neurogenesis, subventricular zone
in
Developmental Neurobiology
volume
84
issue
3
pages
14 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:38616340
  • scopus:85190795438
ISSN
1932-8451
DOI
10.1002/dneu.22939
language
English
LU publication?
yes
id
f216b5b0-0683-4eba-89d4-03eaff220104
date added to LUP
2025-01-08 15:30:47
date last changed
2025-06-26 17:49:33
@article{f216b5b0-0683-4eba-89d4-03eaff220104,
  abstract     = {{<p>Adult neurogenesis continues throughout life but declines dramatically with age and in neurodegenerative disorders such as Alzheimer's disease. In parallel, microglia become activated resulting in chronic inflammation in the aged brain. A unique type of microglia, suggested to support neurogenesis, exists in the subventricular zone (SVZ), but little is known how they are affected by aging. We analyzed the transcriptome of aging microglia and identified a unique neuroprotective activation profile in aged SVZ microglia, which is partly shared with disease-associated microglia (DAM). CX3C motif chemokine receptor 1 (CX3CR1) is characteristically expressed by brain microglia where it directs migration to targets for phagocytosis. We show that Cx3cr1 expression, as in DAM, is downregulated in old SVZ microglia and that heterozygous Cx3cr1 mice have increased proliferation and neuroblast number in the aged SVZ but not in the dentate gyrus, identifying CX3CR1 signaling as a novel age and brain region-specific regulator of neurogenesis.</p>}},
  author       = {{Fritze, Jonas and Muralidharan, Chandramouli and Stamp, Eleanor and Ahlenius, Henrik}},
  issn         = {{1932-8451}},
  keywords     = {{aging; CX3C motif chemokine receptor 1; disease-associated microglia; microglia; neurogenesis; subventricular zone}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{128--141}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Developmental Neurobiology}},
  title        = {{Microglia undergo disease-associated transcriptional activation and CX3C motif chemokine receptor 1 expression regulates neurogenesis in the aged brain}},
  url          = {{http://dx.doi.org/10.1002/dneu.22939}},
  doi          = {{10.1002/dneu.22939}},
  volume       = {{84}},
  year         = {{2024}},
}