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Article

Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism

1
Department of Nutrition and Food Hygiene, School of Public Health, Peking University, No. 38 Xueyuan Road, Beijing 100083, China
2
PKUHSC—China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, No. 38 Xueyuan Road, Beijing 100083, China
3
Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University, No. 38 Xueyuan Road, Beijing 100083, China
*
Author to whom correspondence should be addressed.
Nutrients 2022, 14(6), 1229; https://doi.org/10.3390/nu14061229
Submission received: 9 February 2022 / Revised: 10 March 2022 / Accepted: 11 March 2022 / Published: 14 March 2022
(This article belongs to the Section Nutrition in Women)

Abstract

Recent studies have reported a strong association between gestational diabetes mellitus (GDM) and postpartum depression (PPD), but little is known about the underlying physiological mechanism. In this study, a GDM rat model was used to evaluate the direct effect of GDM on PPD and to explore the mechanism. After parturition, the GDM dams were divided into two groups: blood glucose not recovered group (GH group) and blood glucose recovered group (GL group). Fasting plasma glucose (FPG), cortisol (COR) and serotonin (5-hydroxytryptamine, 5-HT) metabolism were continuously monitored during the lactation period, until postnatal day 21. PPD was evaluated by behavioral tests. At the endpoint, the expression of the key enzymes of Trp metabolic pathway in colon and brain tissues was analyzed by immunohistochemistry and western blot. The microbe composition of colonic contents was determined by 16S rDNA gene sequencing. The results showed that GDM induced postpartum depression-like behavior in rats. The HPA axis hormone did not show the typical stress state of depression, but the level of 5-HT decreased significantly in serum, prefrontal cortex and hippocampus, and the Kyn/Trp ratio increased significantly in serum and prefrontal cortex, implying the switch of the tryptophan (Trp) metabolism from the 5-HT pathway to the kynurenine (Kyn) pathway. The expression of Indoleamine 2,3-dioxygenase (IDO), a key rate-limiting enzyme in Kyn metabolism, was up-regulated in the colon and brain, which was an important reason for this switch. This switch was accelerated by a decrease in the expression of tryptophan hydroxylase (TPH), a key enzyme of the 5-HT production pathway, in the colon. GDM dams displayed significant changes in gut microbiome profiles, which were correlated with depression. The ratio of Firmicutes to Bacteroidetes decreased. Lactobacillus and Bacteroides were negatively correlated with 5-HT level and positively correlated with Kyn level, whereas Clostridium XlVa and Ruminococcus were positively correlated with 5-HT level. These results suggest that GDM disrupts both the Trp pathway and the composition of the gut microbiota, which provide a putative physiological basis for PPD.
Keywords: gestational diabetes mellitus; postpartum depression; tryptophan metabolism; serotonin; kynurenine; gut microbiota gestational diabetes mellitus; postpartum depression; tryptophan metabolism; serotonin; kynurenine; gut microbiota
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MDPI and ACS Style

Zhao, R.; Zhou, Y.; Shi, H.; Ye, W.; Lyu, Y.; Wen, Z.; Li, R.; Xu, Y. Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism. Nutrients 2022, 14, 1229. https://doi.org/10.3390/nu14061229

AMA Style

Zhao R, Zhou Y, Shi H, Ye W, Lyu Y, Wen Z, Li R, Xu Y. Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism. Nutrients. 2022; 14(6):1229. https://doi.org/10.3390/nu14061229

Chicago/Turabian Style

Zhao, Runlong, Yalin Zhou, Hanxu Shi, Wanyun Ye, Ying Lyu, Zhang Wen, Rui Li, and Yajun Xu. 2022. "Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism" Nutrients 14, no. 6: 1229. https://doi.org/10.3390/nu14061229

APA Style

Zhao, R., Zhou, Y., Shi, H., Ye, W., Lyu, Y., Wen, Z., Li, R., & Xu, Y. (2022). Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism. Nutrients, 14(6), 1229. https://doi.org/10.3390/nu14061229

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