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.
Highlights
Major depressive disorder (MDD), known as depression, is a mental disorder characterized by at least two weeks of pervasive low mood
The analysis was conducted by using MATLAB (R2017a) with the results presented in ExpressionOfPPARD in the Supplementary Materials
Peroxisome proliferator-activated receptor beta/delta (PPARD) may activate nitric oxide production (NO) and ceramide, two promoters of MDD. These literature data mining-based relationships suggested that the deficiency of PPARD might facilitate the development of MDD by activating cytokine classes and promoting the secretion of reactive oxygen species (ROS) and glutamate
Summary
Major depressive disorder (MDD), known as depression, is a mental disorder characterized by at least two weeks of pervasive low mood. The leading cause of MDD is believed to be a combination of genetic and environmental factors [1,2,3,4,5,6,7], with about 40% of the risk related to genetics [4]. Peroxisome proliferator-activated receptor beta/delta (PPARD) is one of the three known PPARs (the others are PPARα and PPARγ), which are part of the nuclear receptor superfamily of transcription factors. Several previous studies show that PPARD might be involved in depression occurrences [11, 12]. Hippocampal PPARD overexpression or activation inhibits stress-induced depressive behaviors and enhances neurogenesis [11]. Whether PPARD is involved in MDD and its related underlying mechanism is largely unknown
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