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Loss of Cxcr5 alters neuroblast proliferation and migration in the aged brain

Fritze, Jonas LU ; Ginisty, Aurélie LU ; McDonald, Rebecca ; Quist, Ella LU orcid ; Stamp, Eleanor ; Monni, Emanuela LU ; Dhapola, Parashar LU ; Lang, Stefan LU orcid and Ahlenius, Henrik LU (2020) In Stem Cells 38(9). p.1175-1187
Abstract

Neurogenesis, the production of new neurons from neural stem cells, dramatically decreases during aging concomitantly with increased inflammation both systemically and in the brain. However, the precise role of inflammation and whether local or systemic factors drive the neurogenic decline during aging is poorly understood. Here, we identify CXCR5/5/CXCL13 signaling as a novel regulator of neurogenesis in the aged brain. The chemokine Cxcl13 was found to be upregulated in the brain during aging. Loss of its receptor, Cxcr5, led to increased proliferation and decreased numbers of neuroblasts in the aged subventricular zone (SVZ), together with accumulation of neuroblasts in the rostral migratory stream and olfactory bulb (OB), without... (More)

Neurogenesis, the production of new neurons from neural stem cells, dramatically decreases during aging concomitantly with increased inflammation both systemically and in the brain. However, the precise role of inflammation and whether local or systemic factors drive the neurogenic decline during aging is poorly understood. Here, we identify CXCR5/5/CXCL13 signaling as a novel regulator of neurogenesis in the aged brain. The chemokine Cxcl13 was found to be upregulated in the brain during aging. Loss of its receptor, Cxcr5, led to increased proliferation and decreased numbers of neuroblasts in the aged subventricular zone (SVZ), together with accumulation of neuroblasts in the rostral migratory stream and olfactory bulb (OB), without increasing the amount of new mature neurons in the OB. The effect on proliferation and migration was specific to neuroblasts and likely mediated through increased levels of systemic IL-6 and local Cxcl12 expression in the SVZ. Our study raises the possibility of a new mechanism by which interplay between systemic and local alterations in inflammation regulates neurogenesis during aging.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aging, Cxcl13, Cxcr5, neuroblast, neurogenesis
in
Stem Cells
volume
38
issue
9
pages
1175 - 1187
publisher
Oxford University Press
external identifiers
  • scopus:85086277439
  • pmid:32469107
ISSN
1066-5099
DOI
10.1002/stem.3207
language
English
LU publication?
yes
id
321b9f11-35f8-470c-a638-aee1de3750b2
date added to LUP
2020-07-10 13:58:48
date last changed
2024-03-20 13:27:56
@article{321b9f11-35f8-470c-a638-aee1de3750b2,
  abstract     = {{<p>Neurogenesis, the production of new neurons from neural stem cells, dramatically decreases during aging concomitantly with increased inflammation both systemically and in the brain. However, the precise role of inflammation and whether local or systemic factors drive the neurogenic decline during aging is poorly understood. Here, we identify CXCR5/5/CXCL13 signaling as a novel regulator of neurogenesis in the aged brain. The chemokine Cxcl13 was found to be upregulated in the brain during aging. Loss of its receptor, Cxcr5, led to increased proliferation and decreased numbers of neuroblasts in the aged subventricular zone (SVZ), together with accumulation of neuroblasts in the rostral migratory stream and olfactory bulb (OB), without increasing the amount of new mature neurons in the OB. The effect on proliferation and migration was specific to neuroblasts and likely mediated through increased levels of systemic IL-6 and local Cxcl12 expression in the SVZ. Our study raises the possibility of a new mechanism by which interplay between systemic and local alterations in inflammation regulates neurogenesis during aging.</p>}},
  author       = {{Fritze, Jonas and Ginisty, Aurélie and McDonald, Rebecca and Quist, Ella and Stamp, Eleanor and Monni, Emanuela and Dhapola, Parashar and Lang, Stefan and Ahlenius, Henrik}},
  issn         = {{1066-5099}},
  keywords     = {{aging; Cxcl13; Cxcr5; neuroblast; neurogenesis}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1175--1187}},
  publisher    = {{Oxford University Press}},
  series       = {{Stem Cells}},
  title        = {{Loss of Cxcr5 alters neuroblast proliferation and migration in the aged brain}},
  url          = {{http://dx.doi.org/10.1002/stem.3207}},
  doi          = {{10.1002/stem.3207}},
  volume       = {{38}},
  year         = {{2020}},
}