Fig 1.
Exercise training effect on plasma corticosterone under different intensities of exercise.
Effects of mild exercise (ME) or intense exercise (IE) on plasma corticosterone. Values are expressed as mean ± SE (n = 5). **p<0.01 compared to sedentary control (CONT) rats. ##p<0.01 compared to ME rats. Data were analyzed using a one-way ANOVA, followed by Tukey comparison post-hoc tests.
Fig 2.
Hippocampal neuroanatomical changes induced by different intensities of exercise.
Effects of mild exercise (ME) or intense exercise (IE) on hippocampal DG volume (A), the number of Ki-67+ cells (marker of neuronal progenitor proliferation) (B), BrdU positive cells (marker of cell survival) (C) and BrdU+/NeuN+ cells (marker of newly generate matured neurons) (D). Representative photograph of the dentate gyrus (DG) from each group single-stained for Ki-67 (brown), or double-stained for BrdU (red) and NeuN (green) (E). Values are expressed as mean ± SE (n = 7). * p<0.05; ** p<0.01 compared to sedentary control (CONT) rats. There is no significant difference between both exercise groups in all items. Data were analyzed using a one-way ANOVA, followed by Tukey comparison post-hoc tests.
Fig 3.
Venn diagram of differentially expressed genes in each condition.
The total number of genes modified by ME (gray circles) and IE (white circles) (A), or up- (B) and down- (C) regulated genes in each condition are shown as Venn diagrams. The number in each circle indicates the selection of genes from the total microarray datasets within a defined fold range of greater than 1.5-fold and less than 0.75-fold versus sedentary (CONT).
Fig 4.
The mRNA expression profiles of 13 differentially expressed genes.
Semi-quantitative RT-PCR validation of genes up- or down-regulated with ME or IE in the hippocampus. Each column indicates ME (black columns) or IE (gray columns), respectively. For each gene, the expression change is represented as the fold change in ME or IE relative to CONT. RT-PCR was performed as described in the Methods and the primers are detailed in S2 Table. Gel images on right-side show the PCR product bands stained with ethidium bromide.
Fig 5.
The top three gene-networks in response to mild exercise.
Network analyses of the genes whose expression was modified with ME vs CONT are shown. Major functions of the networks are indicated in 1st (A), 2nd (B) and 3rd (C) network. The score is the negative log of the p value and signifies the possibility of network-eligible genes within a network being clustered together as a result of chance. The biological relationship between two genes is represented as an edge (line), which is supported by at least one reference from the literature or a textbook. The intensity of the node color indicates the degree of up- (red) or down- (green) regulation. Nodes are displayed using various shapes that represent the functional class of the gene product.
Fig 6.
The top three gene networks in response to intense exercise.
Network analyses of the genes whose expression was modified with IE vs CONT are shown. Major functions of the networks are indicated in 1st (A), 2nd (B) and 3rd (C) network. Details are as indicated in Fig 5.
Fig 7.
Hypothetical pathway related to ME-enhanced hippocampal function via AHN.
Genes regulated by ME mapped to the pre-existing signaling pathway based on IPA-modified gene networks and previous literature. The names of up-regulated genes are written in white characters on a black background, those of down-regulated genes are written in black characters on a gray background, and those of unaltered genes are written in black characters on a white background. The genes and pathways related to lipid metabolism (cholesterol-trafficking), protein synthesis and inflammatory response that were up-regulated by ME might be a key to the process of enhancing hippocampal function through increased AHN.
Table 1.
Top five gene functions modified with mild exercise (ME) or intense exercise (IE).