Preprint Article Version 1 This version is not peer-reviewed

Integrative Analysis of Global Gene Expression Identifies Opposite Patterns of Reactive Astrogliosis in Aged Human Prefrontal Cortex

Version 1 : Received: 30 October 2018 / Approved: 31 October 2018 / Online: 31 October 2018 (05:02:17 CET)

A peer-reviewed article of this Preprint also exists.

Payán-Gómez, C.; Rodríguez, D.; Amador-Muñoz, D.; Ramírez-Clavijo, S. Integrative Analysis of Global Gene Expression Identifies Opposite Patterns of Reactive Astrogliosis in Aged Human Prefrontal Cortex. Brain Sci. 2018, 8, 227. Payán-Gómez, C.; Rodríguez, D.; Amador-Muñoz, D.; Ramírez-Clavijo, S. Integrative Analysis of Global Gene Expression Identifies Opposite Patterns of Reactive Astrogliosis in Aged Human Prefrontal Cortex. Brain Sci. 2018, 8, 227.

Journal reference: Brain Sci. 2018, 8, 227
DOI: 10.3390/brainsci8120227

Abstract

Prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the aging cognitive decline and mood changes are not completely understood. In order to improve our knowledge, we integrated transcriptomic data of four studies of human PFC from old people -58-80 years old- compared with young people -20-40 years old- using a meta-analytic approximation combined with molecular signature analysis. We identified 1816 differentially expressed genes -561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of SHH pathway and up-regulation of metallothioneins I and genes of the family EZR -ezrin, radixin, and moesin-. The main conclusions of our study are the confirmation that in aged PFC there is a global dysfunction of the synapses and we reported for the first time opposite phenotypes of astrogliosis because of brain aging.

Subject Areas

prefrontal cortex aging; meta-analysis of transcriptomic; synapsis aging; reactive astrogliosis

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