Identification of a Conserved Gene Signature Associated with an Exacerbated Inflammatory Environment in the Hippocampus of Aging Rats

There have been a few descriptive studies in aged rodents about transcriptome changes in the hippocampus, most of them in males. Here, we assessed the age changes in spatial memory performance and hippocampal morphology in female rats and compared those changes with changes in the hippocampal transc...

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Detalles Bibliográficos
Autores principales: Pardo, Joaquín, Abba, Martín Carlos, Lacunza, Ezequiel, Francelle, Laetitia, Morel, Gustavo Ramón, Outeiro, Tiago F., Goya, Rodolfo Gustavo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2017
Materias:
Bioquímica
Ciencias Médicas
Barnes maze
Aging
Spatial memory
Hippocampal transcriptome
Immune pathways
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/102939
https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.22703
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-102939
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Bioquímica
Ciencias Médicas
Barnes maze
Aging
Spatial memory
Hippocampal transcriptome
Immune pathways
spellingShingle Bioquímica
Ciencias Médicas
Barnes maze
Aging
Spatial memory
Hippocampal transcriptome
Immune pathways
Pardo, Joaquín
Abba, Martín Carlos
Lacunza, Ezequiel
Francelle, Laetitia
Morel, Gustavo Ramón
Outeiro, Tiago F.
Goya, Rodolfo Gustavo
Identification of a Conserved Gene Signature Associated with an Exacerbated Inflammatory Environment in the Hippocampus of Aging Rats
topic_facet Bioquímica
Ciencias Médicas
Barnes maze
Aging
Spatial memory
Hippocampal transcriptome
Immune pathways
description There have been a few descriptive studies in aged rodents about transcriptome changes in the hippocampus, most of them in males. Here, we assessed the age changes in spatial memory performance and hippocampal morphology in female rats and compared those changes with changes in the hippocampal transcriptome. Old rats displayed significant deficits in spatial memory. In both age groups, hole exploration frequency showed a clear peak at hole 0 (escape hole), but the amplitude of the peak was significantly higher in the young than in the old animals. In the hippocampus, there was a dramatic reduction in neurogenesis, whereas reactive microglial infiltrates revealed an inflammatory hippocampal state in the senile rats. Hippocampal RNA‐sequencing showed that 210 genes are differentially expressed in the senile rats, most of them being downregulated. Our RNA‐Seq data showed that various genes involved in the immune response, including TYROBP, CD11b, C3, CD18, CD4, and CD74, are overexpressed in the hippocampus of aged female rats. Enrichment analysis showed that the pathways overrepresented in the senile rats matched those of an exacerbated inflammatory environment, reinforcing our morphologic findings. After correlating our results with public data of human and mouse hippocampal gene expression, we found an 11‐gene signature of overexpressed genes related to inflammatory processes that was conserved across species. We conclude that age‐related hippocampal deficits in female rats share commonalities between human and rodents. Interestingly, the 11‐gene signature that we identified may represent a cluster of immune and regulatory genes that are deregulated in the hippocampus and possibly other brain regions during aging as well as in some neurodegenerative diseases and low‐grade brain tumors. Our study further supports neuroinflammation as a promising target to treat cognitive dysfunction in old individuals and some brain tumors.
format Articulo
Articulo
author Pardo, Joaquín
Abba, Martín Carlos
Lacunza, Ezequiel
Francelle, Laetitia
Morel, Gustavo Ramón
Outeiro, Tiago F.
Goya, Rodolfo Gustavo
author_facet Pardo, Joaquín
Abba, Martín Carlos
Lacunza, Ezequiel
Francelle, Laetitia
Morel, Gustavo Ramón
Outeiro, Tiago F.
Goya, Rodolfo Gustavo
author_sort Pardo, Joaquín
title Identification of a Conserved Gene Signature Associated with an Exacerbated Inflammatory Environment in the Hippocampus of Aging Rats
title_short Identification of a Conserved Gene Signature Associated with an Exacerbated Inflammatory Environment in the Hippocampus of Aging Rats
title_full Identification of a Conserved Gene Signature Associated with an Exacerbated Inflammatory Environment in the Hippocampus of Aging Rats
title_fullStr Identification of a Conserved Gene Signature Associated with an Exacerbated Inflammatory Environment in the Hippocampus of Aging Rats
title_full_unstemmed Identification of a Conserved Gene Signature Associated with an Exacerbated Inflammatory Environment in the Hippocampus of Aging Rats
title_sort identification of a conserved gene signature associated with an exacerbated inflammatory environment in the hippocampus of aging rats
publishDate 2017
url http://sedici.unlp.edu.ar/handle/10915/102939
https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.22703
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