Loss of Cxcr5 alters neuroblast proliferation and migration in the aged brain.
Aging
/ physiology
Animals
Brain
/ physiology
Cell Count
Cell Movement
Cell Proliferation
Cytokines
/ metabolism
Female
Germ-Line Mutation
/ genetics
Lateral Ventricles
/ metabolism
Male
Mice, Inbred C57BL
Microglia
/ metabolism
Neurogenesis
Neurons
/ cytology
Olfactory Bulb
/ metabolism
Receptors, CXCR5
/ metabolism
Cxcl13
Cxcr5
aging
neuroblast
neurogenesis
Journal
Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
03
01
2019
revised:
06
04
2020
accepted:
23
04
2020
pubmed:
30
5
2020
medline:
2
7
2021
entrez:
30
5
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
CXCR5 protein, mouse
0
Cytokines
0
Receptors, CXCR5
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1175-1187Informations de copyright
©2020 The Authors. Stem Cells published by Wiley Periodicals LLC on behalf of AlphaMed Press.
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