Maternal folic acid deficiency stimulates neural cell apoptosis via miR‐34a associated with Bcl‐2 in the rat foetal brain

Abstract

Embryonic development is a critical period wherein brain neurons are generated and organized. Maternal dietary folate, a cofactor in one‐carbon metabolism, modulates neurogenesis and apoptosis in foetal brain neurons. We hypothesized that aberrant neuronal apoptosis may affect the development of the central nervous system during maternal folic acid deficiency, with evident effects because maternal folic acid deficiency modulates the microRNA‐34a associated with Bcl‐2 pathway during embryonic development. Four‐week‐old female Sprague‐Dawley rats were divided randomly into two groups (10 rats per group): a folate‐deficient diet group and a folate‐normal diet group. The diets were administered to the rats 60 d before mating, which was continued for the pregnant dams until parturition. Maternal folic acid deficiency increased neuronal apoptosis in the hippocampus and the cortex in the offspring. Furthermore, maternal folic acid deficiency increased the ratio of cleaved caspase‐3/caspase‐3, followed by an increase in caspase‐3 activity. Moreover, maternal folic acid deficiency downregulated Bcl‐2 and upregulated Bax, and this effect associate with maternal folic acid deficient increases expression of microRNA‐34a. Together, the present results indicate that maternal folic acid deficiency stimulates neuronal apoptosis via microRNA‐34a associated with Bcl‐2 signalling in rat offspring.

Folic Acid Homeostasis and Its Pathways Related to Hepatic Oxidation in Adolescent Rats Exposed to Binge Drinking

“…Moreover, the ratio of cleaved caspase-3/caspase-3 is also reduced, indicating that apoptosis is decreased when FA hepatic levels are balanced, and that this vitamin plays an important role during BD liver damage. FA is known for its anti-apoptotic properties in different types of cells [ 13 , 68 , 69 , 70 , 71 ]. These authors attribute this action to different mechanisms: through decreasing NOX activity-ROS generation- mitochondrial complex II; decreasing OS-, preventing telomeric DNA oxidation and attrition; regulating the expression of apoptosis-related genes (decreased caspase-3 and upregulated BCL2/BAX ratio); modulating microRNA-34a, associated with Bcl-2 signaling; or decreasing caspase-9 activity.…”

Comorbid Conditions in Newborn Operated Due to Open Spinal Dysraphism and Retrospective Evaluation of Relation Between These Situations with Folic Acid Usage During the Pregnancy

“…In an animal study, the present results indicate that maternal folic acid deficiency stimulates neuronal apoptosis via miR-34a (microRNA-34a) associated with Bcl-2 (B-cell lymphoma-2) signalling in brain tissue of rat offspring. These findings provide novel insights into the mechanism of action of maternal folate deficiency in early neurogenesis 10 .…”

Efficient Self-Assembled MicroRNA Delivery System Consisting of Cholesterol-Conjugated MicroRNA and PEGylated Polycationic Polymer for Tumor Treatment

“…To validate the therapeutic efficacy of PEG- g -PEI/cmiR, qRT-PCR was conducted to measure target gene expression of Nanog, Oct3/4, Snail, and Bcl2 by treating HS746T cells with the complexes. The therapeutic efficacy of cmiR delivered by Lipofectamine 2000 (Lipo.2000), a common transfection agent, was validated.…”