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

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.

Folic Acid Preconditioning Alleviated Radiation-Induced Ovarian Dysfunction in Female Mice

“…Thus, we report for the first time the direct relationship between radiation damage to the ovaries and mood change. A previous report demonstrated that FA can regulate emotions in women ( 25 ). We further characterized the regulatory role of FA in radiation-induced mood abnormalities.…”

“…After basic physical examination and confirmation of regular estrous cycles (based on morphological changes in vaginal cytology smears obtained every morning at 8:30 am and observed under a microscope), female mice were randomly assigned to one of four groups: control group (Con), FA pre-administration control group (FA), radiation exposure group (RA), and FA pretreatment + radiation exposure group (RA+FA). FA pre-administration dosage and protocol were selected on the basis of our previous study ( 25 ). Briefly, FA (5 mg/kg; Sigma, St. Louis, MO, USA) was administered daily via gavage.…”

The Problem of Malnutrition Associated with Major Depressive Disorder from a Sex-Gender Perspective

“…The prescription of folic acid during pregnancy is well known, among other things, because of its importance in the development of the fetus and the formation of the neural tube. Recent research correlates this with a lower risk of suffering from psychotic symptoms during pregnancy; in fact, in the animal model that was given doses of 1 and 5 mg/kg of folic acid, this nutrient was postulated as a potential contributor of cognitive alterations in the prenatal stage postpartum [ 247 ]; clinical trials agree with this evidence; thus its supplementation is recommended to reduce the risk of PPD [ 248 ]. This improvement appears to be linked to increased expression of pathways related to neuronal genesis, BDNF and synaptic transmission in the hippocampus [ 247 ].…”

Mangiferin Alleviates Postpartum Depression–Like Behaviors by Inhibiting MAPK Signaling in Microglia

“…Two-month-old female mice were chosen, and hormone-induced pseudopregnancy (HSP)-induced PPD models were established as previously described (Li et al, 2018;Zhang et al, 2021). Mice were randomly divided into four groups (control, PPD, PPD/low MGF, and PPD/high MGF).…”

“…Dramatic changes in postpartum gonadal hormone levels are thought to be an important reason for the occurrence of PPD in the clinic. Based on this theory, multiple studies have established a PPD animal model by injecting progesterone and estrogen to mimic postpartum gonadal hormone changes (Zhang S et al, 2017;Zhu and Tang, 2020;Zhang et al, 2021). However, to date, the potential etiology of PPD has remained unclear, and the regulatory mechanisms are largely unknown.…”