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. 2021 Apr 21:2021:5518138.
doi: 10.1155/2021/5518138. eCollection 2021.

PPARD May Play a Protective Role for Major Depressive Disorder

Tao Yang  1 , Juhua Li  1 , Liyuan Li  1 , Xuehua Huang  1 , Jiajun Xu  1 , Xia Huang  1 , Lijuan Huang  1 , Kamil Can Kural  2
Affiliations

PPARD May Play a Protective Role for Major Depressive Disorder

Tao Yang et al. PPAR Res. .

Abstract

Activation of PPARD has been shown to inhibit depressive behaviors and enhances neurogenesis. However, whether PPARD is involved in the pathological development of major depressive disorder (MDD) is largely unknown. To explore the potential connection between PPARD and MDD, we first conducted a literature-based data mining to construct a PPARD-driven MDD regulating network. Then, we tested the PPARD expression changes in MDD patients from 18 independent MDD RNA expression datasets, followed by coexpression analysis, multiple linear regression analysis, and a heterogeneity analysis to study the influential factors for PPARD expression levels. Our results showed that overexpression of PPARD could inhibit inflammatory cytokine signaling pathways and the ROS and glutamate pathways that have been shown to play important roles in the pathological development of MDD. However, PPARD could also activate nitric oxide formation and ceramide synthesis, which was implicated as promoters in the pathogenesis of MDD, indicating the complexity of the relationship between PPARD and MDD. PPARG presented significant within- and between-study variations in the 18 MDD datasets (p value = 0.97), which were significantly associated with the population region (country) and sample source (p < 2.67e - 5). Our results suggested that PPARD could be a potential regulator rather than a biomarker in the pathological development of MDD. This study may add new insights into the understanding of the PPARD-MDD relationship.

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Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
PPARD-driven pathways involved in the pathology of MDD. The pathway was built through Pathway Studio-assisted literature data mining, supported by over 400 references. The items highlighted in green are the ones that were driven by PPARD to suppress the development of MDD, and the red ones were regulated by PPARD to promote MDD development.
Figure 2
Figure 2
Expression of PPARD in 18 MDD RNA expression datasets: (a) the expression by datasets; (b) the expression by country; (c) the expression by sample source.
Figure 3
Figure 3
Multiple linear regression analysis results for the influential factors of PPARD expression in the cases of major depressive disorder: (a) results for population regions (country); (b) results for sample source.
Figure 4
Figure 4
Error bar plot of the within-study variance of the PPARD expression among 18 major dispersive disorder RNA expression datasets.
See this image and copyright information in PMC

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