title: De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus.
abstract: Aging is accompanied by gradually increasing impairment of cognitive abilities and constitutes the main risk factor of neurodegenerative conditions like Alzheimer's disease (AD). The underlying mechanisms are however not well understood. Here we analyze the hippocampal transcriptome of young adult mice and two groups of mice at advanced age using RNA sequencing. This approach enabled us to test differential expression of coding and non-coding transcripts, as well as differential splicing and RNA editing. We report a specific age-associated gene expression signature that is associated with major genetic risk factors for late-onset AD (LOAD). This signature is dominated by neuroinflammatory processes, specifically activation of the complement system at the level of increased gene expression, while de-regulation of neuronal plasticity appears to be mediated by compromised RNA splicing.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Göttingen Göttingen, Germany ; Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen Göttingen, Germany.
authors.forename: Roman M
authors.initials: RM
authors.lastname: Stilling
authors.affiliation: Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen Göttingen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Benito
authors.affiliation: Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen Göttingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gertig
authors.affiliation: Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen Göttingen, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Barth
authors.affiliation: Research Group for Computational Analysis of Biological Networks, German Center for Neurodegenerative Diseases (DZNE) Göttingen Göttingen, Germany.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Capece
authors.affiliation: Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen Göttingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Burkhardt
authors.affiliation: Research Group for Computational Analysis of Biological Networks, German Center for Neurodegenerative Diseases (DZNE) Göttingen Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bonn
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Göttingen Göttingen, Germany ; Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE) Göttingen Göttingen, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Fischer
keywords: RNA-editing; RNA-seq; gene-environment interaction; inflammaging; innate immune system; learning and memory; neuroinflammation; synaptic plasticity