[Folic acid reduced focal cortical dysplasia of the cerebellum by induction of laminin expression in C57BL/6J mice]

ABSTRACT

Investigation has shown that folic acid supplementation during the critical period of pregnancy is associated with a decrease in the incidence of skeletal, craniofacial and nervous system malformations; and decreasing folic acid during pregnancy results in a range spectrum of malformations. In this study we used an animal model, which displays focal cortical dysplasia around the secunda fissure of cerebellum. This malformation results from ectopic granule cells which proliferate locally just around the bottom of the secunda fissure. Although there are few studies about the effects of folic acid in prevention the risk of neural tube defects, the objective of the present study was to determine whether folic acid is able to decrease the incidence of focal displasya which possibly results from mutation in gene, Cfp-1 located on chromosome 4. If so, there may be a correlation between consumption of folic acid and laminine expression with reduction of percentage of this malformation. Young female C57BL/6J mice were kept under normal conditions and diet and mated. Next day after mating, finding the vaginal plug was designated as day zero of pregnancy and they were divided in three groups. Experimental group 1 received 0.1 mg/kg folic acid from days 7-10 of gestation; experimental group 2 received the same volume of normal saline on the same days; and the control mice were kept untreated. Each group consisted of 8, 7 and 9 animals respecectively. Pregnant mice from gestational days [E17 to E18] to postnatal days [PD 1 to 5] were sacrificed and collected in formaline-acetic-alcohol or 3.7% paraformaldhyde, serially sectioned and stained with Cresyl violet; and selected sections on PD 1 [the day before formation of malformation] were incubated with monoclonal antibody [anti-laminin]. Our findings showed that the percentage of malformations decreased significantly in experimental group 1 [13.8%] compared to experimental group 2 and controls. The rate of laminin expression in folic acid exposed by special regards to secunda fissure increased significantly. These data provide evidence for the ability of folates and their important roles in preventing mice from central nervous system defects. These data might also have significance for human malformations as well