Gene expression changes in aging zebrafish (Danio rerio) brains are sexually dimorphic

Abstract

Background: Brain aging is a multi-factorial process due to both genetic and environmental factors. The zebrafish has recently become a popular model organism for examining aging and age-related diseases because as in humans they age gradually and exhibit cognitive decline. Few studies have examined the biological changes in the aging brain that may contribute to these declines and none have examined them within individuals with respect to gender. Our aim was to identify the main genetic pathways associated with zebrafish brain aging across gender. We chose males and females from specific age groups (young, 7.5-8.5 months and old, 31-36 months) based on the progression of cognitive decline in zebrafish. RNA was isolated from individual brains and subjected to microarray and qPCR analysis. Statistical analyses were performed using a two-way ANOVA and the relevant post-hoc tests.

Results: Our results demonstrated that in the brains of young and old male and female zebrafish there were over 500 differentially expressed genes associated with multiple pathways but most notably were those related to neurogenesis and cell differentiation, as well as brain and nervous system development.

Conclusions: The gene expression of multiple pathways is altered with age and differentially expressed in males and females. Future studies will be aimed at determining the causal relationships of age-related changes in gene expression in individual male and female brains, as well as possible interventions that counteract these alterations.

Figure 1

A Venn diagram showing the number of differentially expressed transcripts. There were 909 transcripts in Male vs Female and 1543 transcripts in Young vs Old comparisons. Two-hundred ten of differentially expressed transcripts were common to both lists.

Figure 2

Relative expression values from microarray and real-time PCR experiments for A) igf1, B) igf2bp3, and C) igfbp2a. Values on the x-axis are the relative expressions in each group. In each graph the value for females are set to 1 as the reference for each group. F; female, M; male, Y; young, O; old. Error bars indicate the standard error, n =?6. *: p < 0.05.

Figure 3

Relative expression values from microarray and real-time PCR experiments for A) ache, B) ppargc1b, and C) lmo4a. Values on the x-axis are the relative expressions in each group. In each graph the value for females are set to 1 as the reference for each group. F; female, M; male, Y; young, O; old. Error bars indicate the standard error, n =?6. *: p < 0.05.

Figure 4

Relative expression values from the microarray and real-time PCR experiments for A) pvalb8 and B) smurf2. Values on the x-axis are the relative expressions in each group. In each graph the value for females are set to 1 as the reference for each group. F; female, M; male, Y; young, O; old. Error bars indicate the standard error, n =?6. *: p < 0.05.