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Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon

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 zebr...

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Autores principales: Zambusi, Alessandro, Pelin Burhan, Özge, Di Giaimo, Rossella, Schmid, Bettina, Ninkovic, Jovica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072227/
https://www.ncbi.nlm.nih.gov/pubmed/32028681
http://dx.doi.org/10.3390/cells9020350
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author Zambusi, Alessandro
Pelin Burhan, Özge
Di Giaimo, Rossella
Schmid, Bettina
Ninkovic, Jovica
author_facet Zambusi, Alessandro
Pelin Burhan, Özge
Di Giaimo, Rossella
Schmid, Bettina
Ninkovic, Jovica
author_sort Zambusi, Alessandro
collection PubMed
description 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.
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spelling pubmed-70722272020-03-19 Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon Zambusi, Alessandro Pelin Burhan, Özge Di Giaimo, Rossella Schmid, Bettina Ninkovic, Jovica Cells Article 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. MDPI 2020-02-03 /pmc/articles/PMC7072227/ /pubmed/32028681 http://dx.doi.org/10.3390/cells9020350 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zambusi, Alessandro
Pelin Burhan, Özge
Di Giaimo, Rossella
Schmid, Bettina
Ninkovic, Jovica
Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon
title Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon
title_full Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon
title_fullStr Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon
title_full_unstemmed Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon
title_short Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon
title_sort granulins regulate aging kinetics in the adult zebrafish telencephalon
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072227/
https://www.ncbi.nlm.nih.gov/pubmed/32028681
http://dx.doi.org/10.3390/cells9020350
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