Maternal folic acid deficiency stimulates neural cell apoptosis via miR-34a associated with Bcl-2 in the rat foetal brain. Issue 72 (February 2019)

• Record Type: Journal Article
• Authors: Li, Wen; Li, Zhenshu; Zhou, Dezheng; Zhang, Xumei; Yan, Jing; Huang, Guowei
• Is Part Of: International journal of developmental neuroscience. Issue 72(2019:Feb.)
• Page Start: 6
• Page End: 12
• Publication Date: 2019-02
• Subjects: NTD neural tube defect -- PND postnatal day -- NSCs neural stem cells -- Bcl-2 B-cell lymphoma-2 -- Bax Bcl-2-associated X protein -- mRNAs MicroRNAs -- miR-34a MicroRNA-34a; Folate deficiency -- Maternal -- miR-34a -- Bcl-2 -- Apoptosis; Developmental neurobiology -- Periodicals; Neurology -- Periodicals; Neurologie du développement -- Périodiques; Developmental neurobiology; Periodicals; 612.8
• DOI: 10.1016/j.ijdevneu.2018.11.002
• Languages: English
• ISSNs: 0736-5748

Abstract

Highlights: Maternal folic acid deficient increased neuronal apoptosis. Maternal folic acid deficiency stimulated the intrinsic apoptotic pathway (Bcl-2 pathway). This effect associate with maternal folic acid deficiency upregulates miR-34a. 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.