Biomedical Engineering Reference
In-Depth Information
Fu et al. (1996) reported studies done in the same laboratory and used
a similar study design and dosing regimen as Sakanashi et al. (1996), but
exposed the pregnant mice to only the higher 2.5 g/kg/day BID metha-
nol dose (total dosage of 5.0 g/kg/day) on GD 6-10. They measured
maternal liver and plasma folate levels on GD 18 and observed similar,
significant reductions in these levels for the FAD versus FAS mice.
However, Fu et al. (1996) also measured fetal liver folate levels at GD
18. Significantly, the maternal FAD diet had a greater impact on fetal
liver folate than maternal liver folate levels on GD 18. Another key
finding in this study was that methanol exposure during GD 6-10 had
similar fetotoxic effects, including cleft palate, exencephaly, and
resorptions, as the same level of methanol exposure administered during
GD 6-15 (Sakanashi et al., 1996; Rogers et al., 1993). This is consistent
with the hypothesis (Rogers and Mole, 1997) that the critical period for
methanol-induced cleft palate and exencephaly in CD-1 mice is within
GD 5-9.
Aziz et al. (2002) investigated the potential role of folic acid in
methanol-induced developmental neurotoxicity in rats. Female albino
Wistar were fed FAD or FAS diets for 14-16 weeks, after which liver
folate levels were estimated and females exhibiting a significantly low
folic acid level were mated. Throughout their lactation period, dams of
both the FAD and FAS groups were given 0%, 1%, 2%, or 4% v/v
methanol via drinking water, equivalent to approximately 480, 960, and
1920mg/kg/day. Pups were exposed to methanol via lactation from
PND 1-21. Liver folate levels were determined at PND 21 and neuro-
behavioral parameters (motor performance using the spontaneous
locomotor activity test and cognitive performance using the conditioned
avoidance response (CAR) test), and neurochemical parameters (dopa-
minergic and cholinergic receptor binding and dopamine levels) were
measured at PND 45. The expression of GAP-43, a protein primarily
localized to growth cone membranes, was examined using immuno-
histochemistry and western blot analysis.
Lower body weight gain was observed at PND 7, 14, and 21 in
animals exposed to 2% or 4%methanol in the FAD group but only at 4%
methanol in the FAS group. Liver folate levels in the FAD group were
decreased by 63% in rats prior to mating and 67% in pups on PND 21.
