The effects of l-cycloserine on gangliosides in the developing mouse brain.

Marked changes in ganglioside composition occur during brain development and in cultured neurons concomitant with differentiation, and maximum ganglioside synthesis occurs during neuronal maturation and synaptogenesis. These findings indicate that gangliosides probably play an important role in brain development. In this study the effects of parenterally administered l-cycloserine (an inhibitor of sphingosine synthesis) on gangliosides during the period of rapid neonatal brain growth in mice were studied. Two groups of mice (saline control and l-cycloserine-20 mg/kg/day) were treated for 8 or 16 days, starting at postnatal day 6, and sacrificed at 14, 22, 32, 62 or 110 days of age. Undernourished controls were also sacrificed at the same times. Body and cerebral weights in the l-cycloserine group were less than those of saline control animals at early ages, but the l-cycloserine animals did not show sparing of cerebral weight in relation to body weight as did the undernourished controls. Compared to saline control animals the l-cycloserine group had significantly less total lipid extract and nonlipid residue over all age groups. Animals treated with l-cycloserine had less total ganglioside NeuNAc per hemisphere, but normal concentrations on a fresh weight basis. Both groups had identical ganglioside patterns. These results indicate that although l-cycloserine does affect some aspects of brain development, it is not useful as a selective inhibitor of ganglioside synthesis in neonatal ICR Swiss Webster mice treated with a dose equivalent to the LD-17. Its value in modifying ganglioside synthesis should be viewed with caution.

Elevation of plasma leptin levels during pregnancy in normal and diabetic women.

The impact of pregnancy and food intake on plasma leptin levels was investigated in insulin-dependent diabetes mellitus (IDDM) patients and healthy normal-weight women. Fourteen women with IDDM and 11 women with no diabetes or family history of diabetes were served a 707-kcal lunch in gestational weeks 34 to 38. Six breast-feeding women from each group were examined a second time within 1 month after delivery. Leptin levels were not different in the two groups either during pregnancy or postpartum. In addition to a positive correlation to body mass index (BMI), leptin levels tended to correlate with gestational weight gain. The leptin concentration during pregnancy was higher than the postpartum level, which was within the range of previously reported levels in non-obese nonpregnant women. Ingestion of the test meal did not affect leptin levels and there were no relationships between leptin and insulin or glucose, for either basal or postprandial (60-minute) levels. Only the insulin dose taken by the diabetic women correlated to leptin level. During pregnancy, there is an augmented energy expenditure and maternal metabolism is altered to increase fat stores. The present observation that leptin levels were elevated in pregnant women suggests an additional role for leptin in the accumulation of body fat.

Ganglioside synthesis and transport in regenerating sensory neurons of the rat sciatic nerve.

The sciatic nerves of rats were crushed with fine forceps and allowed to survive for 3 or 7 days, at which time the 5th lumbar dorsal root ganglion was injected with [3H]glucosamine. Animals were killed 18 h later and the nerves proximal and distal to the crush site were cut into 3 mm segments. Gangliosides were purified from these segments, and radioactivity was separately measured in gangliosides, neutral glycolipids and glycoproteins. For all 3 fractions, radioactivity was distributed similarly between the crush site and point of maximum axonal elongation. A second smaller peak of ganglioside radioactivity was seen to span a few segments immediately distal to the point of maximum axonal elongation. We propose two possible explanations for this: (1) it represents ganglioside synthesis by Schwann cells (from blood-borne [3H]glucosamine) as part of the mitogenic response of these cells to the reappearance of axons; or (2) recently synthesized, transported gangliosides are released from the growth cone and taken up by adjacent mitogenic Schwann cells.

Leptin levels vary significantly during the menstrual cycle, pregnancy, and in vitro fertilization treatment: possible relation to estradiol.

OBJECTIVE: To evaluate the influence of sex steroids on leptin levels in patients with conditions in which the steroid levels are increased. DESIGN: Prospective study. SETTING: A hospital unit for reproductive medicine and a maternal care unit affiliated with the hospital and hospital staff. PATIENT(S): Thirteen women with regular menstrual cycles, 29 women with normal pregnancies, and 25 women undergoing IVF treatment. INTERVENTION(S): Blood samples were obtained during days 1-3, 6-8, 13-15, and 22-25 of the menstrual cycle in regularly cycling women and during gestational weeks 13, 20, 28, 32, and 36 and 7-13 weeks after birth in pregnant women. In women undergoing IVF treatment, blood samples were collected after E2 suppression, after ovarian stimulation, and at the time of ovum pickup. MAIN OUTCOME MEASURE(S): Serum levels of leptin, E2, and progesterone. RESULT(S): Leptin levels varied during the menstrual cycle and were elevated during pregnancy, with a peak during week 28. In the IVF group, leptin levels increased throughout the treatment cycle. Body mass index correlated positively with leptin levels in all three groups, and the maternal weight gain from weeks 13-32 tended to correlate with the rise in leptin levels. Estradiol levels correlated positively with leptin levels during E2 suppression. Negative correlations existed between the pregnancy-induced increases in E2 and leptin levels from weeks 13-32, and between the levels after birth. Leptin levels and progesterone levels did not correlate in any of the groups. CONCLUSION(S): Modest elevations of leptin levels were observed during IVF treatment and pregnancy. The increase in the IVF group indicates that factors other than body fat mass (possibly E2) also are of importance for the regulation of leptin levels.