Meta-analysis of human prefrontal cortex reveals activation of GFAP and decline of synaptic transmission in the aging brain

Acta Neuropathologica Communications
Wasco Wruck, James Adjaye

Abstract

Despite ongoing research efforts, mechanisms of brain aging are still enigmatic and need to be elucidated for a better understanding of age-associated cognitive decline. The aim of this study is to investigate aging in the prefrontal cortex region of human brain in a meta-analysis of transcriptome datasets. We analyzed 591 gene expression datasets pertaining to female and male human prefrontal cortex biopsies of distinct ages. We used hierarchical clustering and principal component analysis (PCA) to determine the influence of sex and age on global transcriptome levels. In sex-specific analysis we identified genes correlating with age and differentially expressed between groups of young, middle-aged and aged. Pathways and gene ontologies (GOs) over-represented in the resulting gene sets were calculated. Potential causal relationships between genes and between GOs were explored employing the Granger test of gene expression time series over the range of ages. The most outstanding results were the age-related decline of synaptic transmission and activated expression of glial fibrillary acidic protein (GFAP) in both sexes. We found an antagonistic relationship between calcium/calmodulin dependent protein kinase IV (CAMK4) and GFAP w...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Neuroanatomy·Liam Anuj O'LearyNaguib Mechawar
Oct 20, 2020·Frontiers in Neurology·Matthew J ReidWendy Noble
Dec 12, 2020·Frontiers in Genetics·Huihui WangYuehua Cui
Feb 10, 2021·Neurochemical Research·Marloes VerkerkeJinte Middeldorp

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Methods Mentioned

BETA
biopsies
PCA

Software Mentioned

R package GOStats
matlines
corrplot
Biogrid
inSilicoMerging
R package forecast
R package
R package factoextra
prcomp
R cor

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