Behavioral effects of prenatal folate deficiency in mice.
BACKGROUND
Folate supplementation decreases the incidence of birth defects such as neural tube defects (NTDs). We and others have shown that gestational dietary folate deficiency that does not produce overt NTDs can alter fetal neural histology. Accordingly, murine offspring were examined for the possible functional consequences of prenatal folate deficiency.


METHODS
CD-1 mice were fed a diet of chow containing 400, 600, or 1200 nmol of folic acid/kg of chow for eight weeks prior to breeding and until GD18, at which time all dams were placed on folate-replete chow. Behavioral tests of male and female offspring included righting reflex, negative geotaxis, forelimb hanging, motor coordination, open field activity, and elevated plus maze activity.


RESULTS
Of greatest significance, the adult offspring that were prenatally folate-deficient exhibited more anxiety-related behavior in the elevated plus maze. Offspring of the 400 nmol of folic acid/kg of chow diet group exhibited significantly shorter durations in the open arms and longer durations in the closed arms. Further, these two behaviors were dose-related. There was also a trend for the prenatally folate-deficient adult mice to exhibit more thigmotaxis (wall-hugging) behavior in the open field, entering the central area less frequently than controls. There were few other differences in tested behaviors between folate-deficient and folate-replete mice.


CONCLUSIONS
Prenatal folate deficiency that is repleted at birth can manifest later with increased anxiety 9-12 weeks after birth.
Ferguson
Sherry A
SA
Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Road, Jefferson, AR 72079, USA. ferguson@nctr.fda.gov
Berry
Kimberly J
KJ
Hansen
Deborah K
DK
Wall
Kelly S
KS
White
Gene
G
Antony
Asok C
AC
D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D005494:Folic Acid Deficiency / Q000503:physiopathology*; D008297:Male; D051379:Mice; D011247:Pregnancy
D005492:Folic Acid