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. 2017 Jun 8;7(1):3044.
doi: 10.1038/s41598-017-03291-x.

Identification of commonly altered genes between in major depressive disorder and a mouse model of depression

Hirotaka Yamagata  1 , Shusaku Uchida  2 , Koji Matsuo  2 , Kenichiro Harada  2 , Ayumi Kobayashi  2 , Mami Nakashima  2   3 , Masayuki Nakano  2   4 , Koji Otsuki  2   5 , Naoko Abe-Higuchi  2 , Fumihiro Higuchi  2 , Toshio Watanuki  2 , Toshio Matsubara  6 , Shigeo Miyata  7 , Masato Fukuda  7 , Masahiko Mikuni  7   8   9 , Yoshifumi Watanabe  2
Affiliations

Identification of commonly altered genes between in major depressive disorder and a mouse model of depression

Hirotaka Yamagata et al. Sci Rep. .

Abstract

The heterogeneity of depression (due to factors such as varying age of onset) may explain why biological markers of major depressive disorder (MDD) remain uncertain. We aimed to identify gene expression markers of MDD in leukocytes using microarray analysis. We analyzed gene expression profiles of patients with MDD (age ≥50, age of depression onset <50) (N = 10, depressed state; N = 13, remitted state). Seven-hundred and ninety-seven genes (558 upregulated, 239 downregulated when compared to those of 30 healthy subjects) were identified as potential markers for MDD. These genes were then cross-matched to microarray data obtained from a mouse model of depression (676 genes, 148 upregulated, 528 downregulated). Of the six common genes identified between patients and mice, five genes (SLC35A3, HIST1H2AL, YEATS4, ERLIN2, and PLPP5) were confirmed to be downregulated in patients with MDD by quantitative real-time polymerase chain reaction. Of these genes, HIST1H2AL was significantly decreased in a second set of independent subjects (age ≥20, age of onset <50) (N = 18, subjects with MDD in a depressed state; N = 19, healthy control participants). Taken together, our findings suggest that HIST1H2AL may be a biological marker of MDD.

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Conflict of interest statement

H.Y. has received a research grant from GlaxoSmithKline. K.M. has received research donations from Otsuka Pharmaceuticals. The aim of this study was to detect biological markers of depression. This study did not assess the effects and/or side-effects of antidepressants. Therefore, the authors have no financial conflicts of interest to declare.

Figures

Figure 1
Figure 1
Venn diagrams of significantly altered genes in patients with MDD-DP and in a mouse model of depression. (a) Comparison of significantly upregulated genes. (b) Comparison of significantly downregulated genes. (c) List of common candidate genes in blood from patients with MDD-DP and a mouse model of depression.
Figure 2
Figure 2
The expression levels of candidate genes in human leukocytes (participants from Experiment 1). Expression levels as dots with average line ± SEM for SLC35A3, PPFIA1, HIST1H2AL, YEATS4, ERLIN2, and PLPP5 mRNA in the leukocytes of patients with MDD-DP and HCs (Experiment 1). *p < 0.05.
Figure 3
Figure 3
The expression levels of candidate genes in murine blood cells, and in murine prefrontal cortex. (a,b) The expression levels of Slc35a3, Ppfia1, Yeats4, Erlin2, and Plpp5 mRNA in non-stressed (NS), chronic, ultra-mildly stressed (CUMS), and CUMS + imipramine-treated mice (IMI) (a; blood cells; NS, N = 6; CUMS, N = 6; IMI, N = 5) (b; PFC; NS, N = 8; CUMS, N = 8; IMI, N = 8). Specific primers for Hist1h2al could not be designed. Plpp5 could not be detected (ND). Data indicate the mean ± SEM. *p < 0.05.
Figure 4
Figure 4
The expression levels of candidate genes in human leukocytes (participants from Experiment 2). The expression levels as dots with average line ± SEM for SLC35A3, PPFIA1, HIST1H2AL, YEATS4, ERLIN2, and PLPP5 mRNA in leukocytes from patients with MDD-DP and HCs (Experiment 2). *p < 0.05.
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