Study Of Maternal Folic Acid Medicate CDK5 And TLR4 Methylation Improve Neurobehavior Development In Rat Offspring

ObjectiveThe maternal nutritional status during pregnancy is associated with the development in offspring,folic acid can participate in many methylation reactions as one carbon unit carrier,while DNA methylation can play an important role in the development of nervous system in offspring.However,whether folic acid intervention during pregnancy can regulate the neural development of offsprings through DNA methylation and its role in specific gene locus is not clearly.In order that,CDK5 and TLR4 methylation level were tested in rat offspring which maternal were intervented by FA,and provide scientific basis for FA reasonable supplementation during pregnancy.MethodsForty-eight mature female Sprague-Dawley rats were randomly assigned into four groups:(1)folic acid deficient diet group(DD group);(2)folic acid normal diet group(ND group);(3)folic acid supplementation diet short period group(FD-S group);(4)folic acid supplementation diet long period group(FD-L group).The day of delivered was recored as the PD1,during PD1-PD14,body weight of neonatal rats were monitored;Standard day of physiological development paraments were recorded;Surface righting reflex,negative geotaxis reflex,forelimb grip test,cliff avoidance test and sensory reflexes were used to test the development of neurobehavioral.The concentration of serum FA,plasma Hcy,plasma SAM and SAH were tested in maternal;The concentration of FA was tested in dam serum and brain,the concentration of Hcy,SAM,SAH,the activity of DNMTs and 5-mc% were tested in dam brain;The methylation level of CDK5 and TLR4 promoter and expression level were tested in dam brain.ResultsFA intervention during pregnant has an effect on body weight of female dam in early time(P<0.05),but there was no significant changes in physiological development paraments.FA deficiency during pregnancy can delay the nerve reflex behavior in offspring,FA supplementation can improve the performance.FA supplementation during pregnant can increase the folate,decrease the Hcy and SAM,increase SAM/SAH in brain tissue of dam,FA deficiency during pregnant can decrease the folate,increase the Hcy and SAM,decrease SAM/SAH in brain tissue of dam(P<0.05);FA supplementation during pregnant can increase the expression and activity of DNMTs and the total DNA mathylation level in brain tissue of dam,while FA deficiency during pregnant can decrease its level(P<0.05);FA supplementation during pregnant can increase the methylation level of CDK5 and TLR4 promoter,decrease the expression of CDK5 and TLR4 in brain tissue of dam,while FA deficiency during pregnant can decrease the methylation level of CDK5 and TLR4 promoter,increase its expression(P<0.05).ConclusionIn conclusion,FA supplementation during pregnant can improve the neurobehavioral development in rat offsprings.FA supplementation during pregnant can improve the level of folic acid and SAM,decrease the level of Hcy and SAH and improve the the potential of methylation,while improve the activity of DNMTs and the level of total DNA methylation in the brain of offsprings.FA supplementation during pregnancy increased the methylation level of CDK5 and TLR4 gene promoter,so that silence the expression of CDK5 and TLR4 in the brain of offsprings.FA supplementation during pregnancy can improve neurobehavioral development in rat offsprings through medicating the methylation level of CDK5 and TLR4 gene.