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EC number: 203-710-0
CAS number: 109-83-1
The daily food intake and body weight gainof the pregnant rats
fed the various diets, and the rate of survival of newborn pups are
shown in Table 1. The amount of food ingested by the CD, CS and DME
groups of dams was the same, while the intake of the MME group was only
about 40% of that of the others. The daily gain in body weight of the
dams reflected this intake of the diets. Gestation proceeded normally in
all the pregnant rats. Litters of approximately equal size (average of
12) were delivered by the dams, but the average body weight of the pups
born of the MME group of dams was significantly lower than that of the
other litters. It is worth noting that the gain in body weight of dams
fed the CD, CS and DME diets, as well as the body weight of their
respective pups, were comparable to those of dams, and their pups, fed
laboratory chow (LC). It is apparent, therefore, that the synthetic
diets are fairly adequate even though they lack Ch, and contain only
marginal amounts of methionine. All the pups delivered by the dams fed
the LC, CD and CS diets survived for more than I5 days.In contrast,
only 18 out of 253, and none out of 120, survived for more than 36 h in
the groups of pups delivered by mothers fed the DME and MME diets,
No significant histological or cytological abnormalities were seen in
the brains of pups born of dams fed the various diets. Heavy deposits of
glycogen were seen in the livers of pups born of dams fed the CS diet.
In the liver of pups born of dams fed the MME and DME diet, glycogen and
fatty infiltrations of moderate degrees were present.
Brain and liver weight
As seen in Table 2, apart from the MME pups, the weights of liver and
brain in all the other dietary categories of pups were quite similar
within one representative experimental group of animals.
Brain and liver DME, Ch and ACh
As shown in Fig. 1 (attached document), day-old MME- and DMEexposed pups
had measurable amounts of DME in their brains (11.7±1.8
and 72.7±12.7nmol/g, respectively), while DME was not
detectable in the brains of pups born of dams fed the CD and CS diets.
The brain level of Ch was elevated 43% in the MME-exposed and 53% in the
DME-exposed pups when compared with that in pups born of dams fed the CD
diet. Levels of ACh in the brain were also increased by 27% in the
MME-exposed pups, and by 36% in the DME-exposed pups. Concentrations of
Ch and ACh in the brains of the day-old pups born of dams fed the CS
diet, while elevated, did not differ significantly from those of the
pups in the CD group of dams (t = 1.4839, df = 10, P > 0.2) but Ch
levels were significantly lower than those of pups in the MME and DME
exposed groups of pups.
Figure 2 shows the concentrations of DME, Ch and ACh in the livers of
the pups. From a comparison of Figs. 1 and 2, it is apparent that the
four diets led to liver profiles of DME, Ch, and ACh qualitatively
similar to those in the brain. However, there was one quantitative
difference. In the pups of the CS group of dams, the liver content of Ch
was significantly higher than that in the pups of the CD group, whereas
the brain Ch content was not.
The concentrations of DME, Ch and ACh, which were measured separately in
the cortex and striatum of the dams, are shown in Table 3. As was the
case with the pups, DME was present in the brain tissues of both the MME
and DME groups of dams but not in the CD or CS groups. The concentration
of DME in the brain areas of the DME-treated dams was, however, approx
30-fold higher than that of the MME-treated dams. Unlike the whole brain
Ch levels in the pups, the Ch content in both brain areas of the CS and
MME groups of dams was not different from that of the CD group. The Ch
concentration in the DME-treated dams brain areas could not accurately
be determined because of methodologic complications in measuring Ch
content in the presence of tissue concentrations of DME 10-fold greater
than those of Ch (for discussion see Zahniser et al., 19776). Also, in
contrast with the results of the pup brain ACh determinations, the
cortical and striatal levels of ACh in the CS, MME and DME groups of
dams were similar when compared with those of the CD group.
Table 4 shows that there was no striking difference between the various
groups of pups in either the concentration or the content of brain total
phospholipids. The concentration of total phospholipid in brains of the
CS group of pups was significantly lower (P<0.05) than that in the CD
pups, but this difference amounted to only 11%. Significant differences
did, however, exist in the relative content of the individual
phospholipids. The contents of sphingomyelin and phosphatidic acids in
pups of dams fed the CD diet were lower than those in pups born of
mothers fed the other diets.In pups of mothers fed the MME or DME
diets, the contents of phosphatidyl-Ch and phosphatidylaminoethanol
(PAE) were markedly lower than those in pups delivered by dams fed
either the CD or CS diets.Large amounts of PMME and PDME were
present in the brain phospholipids of the MME-exposed pups and PDME in
the DME-exposed pups. Other phospholipids examined were equally
distributed in the various groups of pups.
" Pregnant rats were fed for 15 days predelivery until 15 days
postpartum a choline (Ch)-deficient diet (CD diet) or a CD diet
supplemented with 0.8% Ch-CI (CS), 1% N-methylaminoethanol (MME) or I %
N,N-dimethylaminoethanol (DME). Gestation and parturition of the
pregnant rats proceeded normally. However, all the pups born of dams fed
the MME diet, and most of those born of dams fed the DME diet, died
within 36 h of birth. No histological or cytological alterations were
detected in the brain of the pups. Levels of Ch and acetylcholine (ACh)
were elevated in the brain of pups born of dams fed the MME and DME
diets, but not the CS diet. The content of total phospholipids in the
brain of the pups was not altered by the diet fed to the dams. However,
the phosphatidyl-Ch and phosphatidylaminoethanol (PAE) contents in the
brain of the MME- and DMEexposed pups were markedly reduced. At the same
time, significant amounts of DME, phosphatidyl-Nmonomethylaminoethanol
(PMME) and of phosphatidyl-N,N-dimethylaminoethanol( PDME) were present
in the same brain areas."
"It has been concluded that, in the presence of a dietary deficiency of
Ch, MME increases the demand for methyl groups and is thus more toxic
than DME which is already two-thirds methylated. Our observations (Table
1) support this conclusion in as much as supplementation of the CD diet
with 1% MME, but not with 1% DME, appears to compromise the growth of
the dams as well, and indicates that availability of methyl groups may
be the critical factor."
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