Gestational Folic Acid Administration Alleviated Maternal Postpartum Emotional and Cognitive Dysfunction in Mice.

Qianyu Zhang,Lin Fan,Fenghua Liu,Hao Li,Xiqian Zhang,Songlu Wang,Yingqi Nong,Li Sun,Jianxing Ruan,Qianwen Huang,Jinyan Wei,Ye Chen,Yan Zhang,Wenjuan Liu,Li Yao

doi:10.3389/fphar.2021.701009

Qianyu Zhang, Lin Fan + Show 13 more

Open Access

https://doi.org/10.3389/fphar.2021.701009

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Abstract

Gestational folic acid (FA) supplementation has been widely recognized for its benefits in preventing offspring defects, but its effect on postpartum females has not yet been adequately assessed. The occurrence of emotional and cognitive dysfunction is common in postpartum women, and its treatment remains limited. Considering the promising results of FA in various psychiatric disorders both in human and redents, we tested the effect of gestational FA administration on postpartum psychiatric behavioral phenotypes and the implicated brain-related mechanisms in a murine model. FA was administered orally in both the hormone-stimulated-pregnancy (HSP) model and pregnant mice at doses of 1 and 5 mg/kg. Postpartum behavioral results showed that the disorders of cognitive performance, depressive, and anxiety-related behaviors were all alleviated in the 5 mg/kg FA group. However, the general development of their offspring remained unaffected. Immunofluorescence and immunoblot results revealed that FA pretreatment significantly activated the maternal hippocampal BDNF-related pathway. Morphological studies have confirmed that FA promotes hippocampal neurogenesis. Moreover, synaptic plasticity and synaptic transmission are enhanced. All of these hippocampal changes play critical roles in rescuing neuronal function and behaviors. Thus, our data suggest that gestational FA administration has a therapeutic effect that improves cognition and reduces depression and anxiety in a murine postpartum model. This may be developed as a preventive and adjuvant therapeutic option for pregnant women.

Highlights

Women who undergo pregnancy and childbirth experience dramatic hormonal fluctuations, which contribute to the occurrence of mental symptoms, including cognitive and emotional dysfunction, as are widely observed in postpartum women
Impaired cognition was observed in the Y-maze test and novel object recognition memory in HSP female mice compared with the Sham-treated OVX control, while the total number of entries and object recognition during familiarization phase had little changes. (Figures 1D,E)
In the EPM test, the trajectory diagram showed that the time in the open arms and the number of entries were markedly reduced in the HSP group compared to the control group (Figures 1H,I)

Summary

Introduction

Women who undergo pregnancy and childbirth experience dramatic hormonal fluctuations, which contribute to the occurrence of mental symptoms, including cognitive and emotional dysfunction, as are widely observed in postpartum women. The incidence and prevalence of unique symptoms occurring after birth range from 8 to 26%, and multiple symptoms are often found concurrently These symptoms in postpartum women are often overlooked, leading to lower diagnosis rates and even lower treatment rates. These symptoms affect the quality of life of postpartum women, and mother-infant interactions and spousal relationships, which in turn affect child-rearing behaviors and healthy development of infants. Therapies that can serve as complementary or alternative treatments must be developed

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