Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon.
Aging
/ metabolism
Aging, Premature
/ genetics
Animals
Cell Differentiation
Gene Expression Profiling
Intercellular Signaling Peptides and Proteins
/ deficiency
Kinetics
Microglia
/ metabolism
Mutation
/ genetics
Neurogenesis
/ genetics
Oligodendroglia
/ metabolism
Phenotype
Stem Cells
/ metabolism
Telencephalon
/ metabolism
Telomere
/ metabolism
Transcriptome
/ genetics
Zebrafish
/ genetics
Zebrafish Proteins
/ deficiency
aging
granulin
microglia
neurogenesis
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
03 02 2020
03 02 2020
Historique:
received:
19
12
2019
revised:
31
01
2020
accepted:
31
01
2020
entrez:
8
2
2020
pubmed:
8
2
2020
medline:
13
2
2021
Statut:
epublish
Résumé
Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.
Identifiants
pubmed: 32028681
pii: cells9020350
doi: 10.3390/cells9020350
pmc: PMC7072227
pii:
doi:
Substances chimiques
Intercellular Signaling Peptides and Proteins
0
Zebrafish Proteins
0
progranulin A, zebrafish
0
progranulin B, zebrafish
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
Abbreviations
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