Folate and Folate-Dependent Enzymes Associated with Rat CNS Development

Abstract

Folic acid and its derivatives are important mediators in growth-related cellular processes. The concentration of folate and two folate-dependent enzymes, 10-formyltetrahydrofolate synthetase (10-FTHFS) and 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH), was determined in brain regions over the early period of rat development. Folate concentrations determined at birth were high in all brain regions studied. During the first 2 weeks, folate concentrations declined steadily, followed by a period of significant increase. High and invariant activity of 10-FTHFS was found throughout the period of study. Low amounts of 10-FTHFDH were seen for the first 2 weeks, but increased significantly from postnatal days 14 to 28. These changes correlated with changes determined in the concentration of folate, supporting the idea that this protein is involved with folate uptake and/or storage. Furthermore, immunohistochemical expression of 10-FTHFDH in different rat brain regions revealed glial cells as a preferential cellular location for this folate-binding protein.

Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study

“…It is intriguing that the third quartile of red blood cell folate levels (1538–1813 nmol/L) seems to be the optimum for embryonic cerebellar growth of which the implications for fetal cerebellar growth and future neurodevelopmental outcome needs further investigation. This first study investigating associations between periconceptional folate status and human embryonic cerebellar size and growth trajectories may substantiate to previous animal studies showing alterations in cerebellar growth and development in a folic acid deficient environment [ 27 , 31 , 32 ]. Besides, our results are in agreement with previous human studies demonstrating significant positive effects of periconceptional maternal folic acid supplement use and folate status on embryonic and fetal size [ 12 , 20 , 30 ] and DNA methylation of the growth gene IGF2 DMR [ 33 , 34 ].…”

Behavioral effects of prenatal folate deficiency in mice

“…This difference may reflect an impact of folate deficiency on postnatal brain development. In fact, endogenous folate levels reflect such a window of sensitivity as well, with high folate concentrations in the rat frontal and occipital cortex, caudate/putamen, and cerebellum at birth, which then steadily decline over the next three postnatal weeks (Martinasevic et al, 1999), indicating that postnatal folate deficiencies might further impact brain development.…”

Folate Supplementation in Rats: Does it Cause Behavioural and Electrophysiological Changes?

“…Folic acid has become very popular since the early 1990s, mainly due to the report that supplementation of the diet with the vitamin during the periconception-al period and in early pregnancy can reduce the incidence of congenital abnormalities, like neural-tube defects (4)(5)(6). Additionally, there is now agreement that subnormal folate supply is associated with hyperhomocysteinaemia, recently confirmed as a new risk factor for cardiovascular disease (7,8).…”