Effect of folic acid on prenatal alcohol-induced modification of brain proteome
Yajun Xu*, Yunan Tang and Yong Li
Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100083, China
(Received 19 December 2006 – Revised 5 July 2007 – Accepted 5 July 2007)
Maternal alcohol consumption during pregnancy can induce central nervous system abnormalities in the fetus, and folic acid supplementation can
reverse some of the effects. The objective of the present study was to investigate prenatal alcohol exposure-induced fetal brain proteome alteration
and the protective effect of folic acid using proteomic techniques. Alcohol (5·0g/kg) was given intragastrically from gestational day (GD) 6 to15,
with or without 60·0mg folic acid/kg given intragastrically during GD1–16 to pregnant Balb/c mice. The control group received distilled water
only. Results of litter evaluation on GD18 showed that supplementation of folic acid reversed the prevalence of microcephaly induced by alcohol.
Proteomic analysis indicated that, under the dosage of the present investigation, folic acid mainly reversed the alcohol-altered proteins involved in
energy production, signal pathways and protein translation, which are all important for central nervous system development.
Alcohol: Folic acid: Brain proteome: Fetal alcohol syndrome
The toxic effect of maternal alcohol consumption during
pregnancy has been documented over the last two decades
since Jones & Smith first described the characteristics of fetal
alcohol syndrome (FAS) in 19731. As a result of these studies,
genital neurological abnormalities is well established2–4.
Microcephaly, defined as reduced brain weight relative to
body weight, is a classic indicator of central nervous system
(CNS) malformation, which is central to a diagnosis of FAS5.
cognitive and psychosocial functioning6–9. The most frequent
problems include attention deficit, sequential processing
(short-term memory and encoding) impairment, neuropsychia-
tric abnormalities and hyperactivity, which might contribute to
the likelihood of committing crimes10,11.
Animal models of FAS have been used successfully to
examine the effect of alcohol exposure during development
on social behaviour. It has been shown that prenatal alcohol
exposure affects the learning and memory abilities, and the
executive functioning of rodents3,12,13. The social behaviour
deficits found in rodent pups following perinatal alcohol
exposure were consistent with the frequently observed clinical
symptoms in FAS children14.
Folic acid (FA) has been credited with a beneficial role in
preventing a range of birth defects, especially neurological
abnormalities15–18. Lalonde et al.19also found that increases
in the plasma level of FA decreased perseverative respond-
ing and improved spatial memory in rats. In the present
investigation, we studied the effect of FA on prenatal alco-
hol-induced fetal brain proteome modification in mice,
hoping to provide a molecular clue to the protective mechan-
ism of FA on alcohol-related abnormalities in the CNS.
Materials and methods
Anhydrous ethanol was purchased from the Beijing Chemical
Company (Beijing, China). FA was purchased from the Sigma
Chemical Company (St Louis, MO, USA). Acrylamide,
ammonium persulfate, isoelectric pH gradient strips (5mm
wide, 18cm long, pH 3–10 linear), urea, and ultrapure
reagents for polyacrylamide gel preparation were obtained
from Bio-Rad (Hercules, CA, USA). Carrier ampholytes (pH
4–8) and 3-[(3-cholamidopropyl) dimethylammonio]-1-pro-
pane sulfonate (CHAPS) were also obtained from Bio-Rad.
iodoacetamide, ammonium bicarbonate, trifluoroacetic acid
and a-cyano-4-hydroxycinnamic acid were obtained from
the Sigma Chemical Company. Modified porcine trypsin was
purchased from Promega (Madison, WI, USA). All chemicals
(unless specified) were reagent grade and used without further
purification. High-purity water was prepared from a Milli-Q
gradient water-purification system (Millipore, Bedford, MA,
USA) and was used for proteome analysis in the present study.
*Corresponding author: Dr Yajun Xu, fax þ86 10 82801575, email firstname.lastname@example.org
Abbreviations: CNS, central nervous system; FA, folic acid; FAS, fetal alcohol syndrome; GD, gestational day; TCTP, translationally controlled tumour protein.
British Journal of Nutrition (2008), 99, 455–461
q The Authors 2007
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Alcohol, folic acid and fetal brain proteome461
British Journal of Nutrition