Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes
Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor,...
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doaj-0175186ab5fe4f0bb1851809ab0a959b2020-11-25T02:24:39ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652017-05-01910.3389/fnagi.2017.00162255855Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron SubtypesLeon French0Leon French1Leon French2TianZhou Ma3Hyunjung Oh4George C. Tseng5Etienne Sibille6Etienne Sibille7Etienne Sibille8Neurobiology of Depression and Aging Lab, Centre for Addiction and Mental Health, Campbell Family Mental Health Research InstituteToronto, ON, CanadaDepartment of Psychiatry, University of TorontoToronto, ON, CanadaInstitute of Medical Science, University of TorontoToronto, ON, CanadaDepartment of Biostatistics, University of PittsburghPittsburgh, PA, United StatesNeurobiology of Depression and Aging Lab, Centre for Addiction and Mental Health, Campbell Family Mental Health Research InstituteToronto, ON, CanadaDepartment of Biostatistics, University of PittsburghPittsburgh, PA, United StatesNeurobiology of Depression and Aging Lab, Centre for Addiction and Mental Health, Campbell Family Mental Health Research InstituteToronto, ON, CanadaDepartment of Psychiatry, University of TorontoToronto, ON, CanadaDepartment of Pharmacology and Toxicology, University of TorontoToronto, ON, CanadaGenome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst) neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6) and in the vasoactive intestinal peptide (Vip) neuron subtype expressing myosin binding protein C, slow type (Mybpc1). These findings provide new insights into cell specific susceptibility to normal aging, and suggest age-related synaptic changes in specific inhibitory neuron subtypes.http://journal.frontiersin.org/article/10.3389/fnagi.2017.00162/fullgene expressioncell-type specifictranscriptomeagingneuroinformaticssynapse |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leon French Leon French Leon French TianZhou Ma Hyunjung Oh George C. Tseng Etienne Sibille Etienne Sibille Etienne Sibille |
spellingShingle |
Leon French Leon French Leon French TianZhou Ma Hyunjung Oh George C. Tseng Etienne Sibille Etienne Sibille Etienne Sibille Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes Frontiers in Aging Neuroscience gene expression cell-type specific transcriptome aging neuroinformatics synapse |
author_facet |
Leon French Leon French Leon French TianZhou Ma Hyunjung Oh George C. Tseng Etienne Sibille Etienne Sibille Etienne Sibille |
author_sort |
Leon French |
title |
Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes |
title_short |
Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes |
title_full |
Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes |
title_fullStr |
Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes |
title_full_unstemmed |
Age-Related Gene Expression in the Frontal Cortex Suggests Synaptic Function Changes in Specific Inhibitory Neuron Subtypes |
title_sort |
age-related gene expression in the frontal cortex suggests synaptic function changes in specific inhibitory neuron subtypes |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2017-05-01 |
description |
Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst) neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6) and in the vasoactive intestinal peptide (Vip) neuron subtype expressing myosin binding protein C, slow type (Mybpc1). These findings provide new insights into cell specific susceptibility to normal aging, and suggest age-related synaptic changes in specific inhibitory neuron subtypes. |
topic |
gene expression cell-type specific transcriptome aging neuroinformatics synapse |
url |
http://journal.frontiersin.org/article/10.3389/fnagi.2017.00162/full |
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