Abstract:
Folates are crucial in the entire process of pregnancy, and their deficiency can result in
congenital diseases such as spina bifida (SB), which are often comorbid with
hydrocephalus (HC). Maternal folic acid supplements can precipitate the incidence of
hydrocephalus in neonates, and any fault in the folic acid metabolism can prevent the
growing embryo from receiving the bioactive folates required for cellular processes. This
highlights a need to look for something more promising than folic acid supplementations.
We aimed to identify and compare the preventative impact of synthetic and bioactive
maternal folate supplements on CNS in an animal model of SB-HC comorbidity generated
through valproic acid. Three maternal folate supplements were selected: folic acid
(synthetic folate), folinic acid (bioactive folate), and folinic acid+ 5-methyltetrahydrofolate
(5-mTHF) (mixture of bioactive folates). The gross appearance and morphological study
of the fetuses revealed hydrocephalus precipitation in the folic acid group, which was best
prevented by the treatment of folinic acid+5-mTHF. Cerebral folate expression was
increased, and methylation levels were decreased in the folic acid group. This indicates
that the folates have not been utilized in the DNA and RNA methylation, which is necessary
for cerebral development. The activity of cerebral folate receptor alpha was also reduced
in the folic acid group. The best preventative effects regarding folate utilization,
methylation, and folate receptor activity were observed in the case of folinic acid+5-mTHF.
The data indicates that bioactive folates, especially a mixture of folinic acid and 5-mTHF,
outperform synthetic folate in the prevention of SB-HC comorbidity.
