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. 2018 Apr 1;28(4):1272-1281.
doi: 10.1093/cercor/bhx040.

Inter-Regional Variations in Gene Expression and Age-Related Cortical Thinning in the Adolescent Brain

Angelita Pui-Yee Wong  1   2 , Leon French  3   4 , Gabriel Leonard  5 , Michel Perron  6   7 , G Bruce Pike  8 , Louis Richer  7 , Suzanne Veillette  6   7 , Zdenka Pausova  9 , Tomáš Paus  1   2   4   10
Affiliations

Inter-Regional Variations in Gene Expression and Age-Related Cortical Thinning in the Adolescent Brain

Angelita Pui-Yee Wong et al. Cereb Cortex. .

Abstract

Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2). Across 34 cortical regions (Desikan-Killiany parcellation), age-related cortical thinning varied as a function of mRNA expression levels of NR3C1 in males (R2 = 0.46) and females (R2 = 0.30) and AR in males only (R2 = 0.25). Cortical thinning did not vary as a function of expression levels of PGR, ESR1, or ESR2 in either sex; this might be due to the observed low consistency of expression profiles of these 3 genes across donors. Inter-regional levels of the NR3C1 and AR expression interacted with each other vis-à-vis cortical thinning: age-related cortical thinning varied as a function of NR3C1 mRNA expression in brain regions with low (males: R2 = 0.64; females: R2 = 0.58) but not high (males: R2 = 0.0045; females: R2 = 0.15) levels of AR mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.

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Figures

Figure 1.
Figure 1.
The mRNA expression levels for the NR3C1, AR, PGR, ESR1, and ESR2 genes. Note: Relative to each specific gene, red regions represent regions with the highest expression levels and blue regions represent regions with the lowest expression levels.
Figure 2.
Figure 2.
Inter-regional age-related cortical thinning as a function of inter-regional mRNA expression levels of NR3C1, AR, PGR, ESR1, and ESR2 genes. The relationship between cortical thickness and age varied negatively as a function of NR3C1 mRNA expression levels in both males and females (A). The relationship between cortical thickness and age varied negatively as a function of AR mRNA expression levels in males only (B). The relationship between cortical thickness and age did not vary as a function of PGR, ESR1, nor ESR2 mRNA expression levels (C, D, and E, respectively). Note: within each subfigure, each point represents 1 of the 34 cortical regions.
Figure 3.
Figure 3.
The interaction of NR3C1 and AR mRNA expression levels. There was a significant NR3C1 and AR interaction in males and in females. In both males and females, inter-regional age-related cortical thinning varied as a function of inter-regional NR3C1 mRNA expression levels in the low AR mRNA expression group, but not the high AR mRNA expression group. Note: within each subfigure, each point represents 1 of the 34 cortical regions.
See this image and copyright information in PMC

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