IDENTIFICATION OF A CONSERVED GENE SIGNATURE ASSOCIATED WITH AN EXACERBATED INFLAMMATORY ENVIRONMENT IN THE HIPPOCAMPUS OF AGING RATS

PARDO J; ABBA M; LACUNZA E; FRANCELLE L; MOREL GR; OUTEIRO T; GOYA RG

HIPPOCAMPUS

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2017 vol. 4 p. 435 - 449

1050-9631

There have been a few descriptive studies in aged rodents about transcriptome changes in thehippocampus, most of them in males. Here, we assessed the age-changes in spatial memoryperformance and hippocampal morphology in female rats and compared those changes withchanges in the hippocampal transcriptome. Old rats displayed significant deficits in spatialmemory. In both age groups hole exploration frequency showed a clear peak at hole 0 (escapehole), but the amplitude of the peak was significantly higher in the young than in the oldanimals. In the hippocampus there was a dramatic reduction in neurogenesis, whereas reactivemicroglial infiltrates revealed an inflammatory hippocampal state in the senile rats.Hippocampal RNA-sequencing showed that 210 genes are differentially expressed in thesenile rats, most of them being downregulated. Our RNA-Seq data showed that various genesinvolved in the immune response, including TYROBP, CD11b, C3, CD18, CD4 and CD74,are overexpressed in the hippocampus of aged female rats. Enrichment analysis showed thatthe pathways overrepresented in the senile rats matched those of an exacerbated inflammatoryenvironment, reinforcing our morphologic findings. After correlating our results with publicdata of human and mouse hippocampal gene expression, we found an 11-gene signature ofoverexpressed genes related to inflammatory processes that was conserved across species. Weconclude that age-related hippocampal deficits in female rats share commonalities betweenhuman and rodents. Interestingly, the 11-gene signature that we identified may represent acluster of immune and regulatory genes that are deregulated in the hippocampus and possiblyother brain regions during aging as well as in some neurodegenerative diseases and low-gradebrain tumors. Our study further supports neuroinflammation as a promising target to treatcognitive dysfunction in old individuals and some brain tumors.