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Age-related changes in function and gene expression of the male and female mouse bladder.

ABSTRACT: We investigated age-related changes in in vivo and in vitro functions and gene expression of the bladder of male and female mice. Mature and aged (12 and 27-30 month old) C57BL/6 mice of both sexes were used. Frequency volume, conscious free-moving cystometry and detrusor contractile and relaxant properties in in vitro organ bath were evaluated. mRNA expression level of muscarinic, purinergic, and β-adrenergic receptors and gene expression changes by cDNA microarray analysis of the bladder were determined. Cystometry demonstrated storage and voiding dysfunctions with ageing in both sexes. Detrusor strips from aged mice showed weaker contractile responses particularly in the cholinergic component and weaker relaxant responses to isoproterenol. These age-related impairments were generally severer in males. mRNA expression of bladder tissue was decreased for M3 muscarinic receptors in aged males and β2-adrenoceptors in aged females. cDNA microarray analysis results, albeit substantial sex difference, indicated "cell-to-cell signaling and interaction" as the most common feature of age-related gene expression. In summary, aged mice demonstrated voiding and storage dysfunctions resembling to detrusor hyperactivity with impaired contractility (DHIC), which were more pronounced in males. Genomic changes associated with aging may contribute to the age-related bladder functional deterioration in mice.

SUBMITTER: Kamei J

PROVIDER: S-EPMC5794976 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project 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.

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Age-related changes in function and gene expression of the male and female mouse bladder.

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