In vivo magnetic resonance spectrometry imaging demonstrates comparable adaptation of brain energy metabolism to metabolic stress induced by 72 h of fasting in depressed patients and healthy volunteers.

Major depressive disorder (MDD) is characterized by dysregulation of stress systems and by abnormalities in cerebral energy metabolism. Stress induction has been shown to impact neurometabolism in healthy individuals. Contrarily, neurometabolic changes in response to stress are insufficiently investigated in MDD patients. Metabolic stress was induced in MDD patients (MDD, N = 24) and in healthy individuals (CTRL, N = 22) by application of an established fasting protocol in which calorie intake was omitted for 72 h. Both study groups were comparable regarding age, gender distribution, and body mass index (BMI). Fasting-induced effects on brain high-energy phosphate levels and membrane phospholipid metabolism were assessed using phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Two-way repeated measures ANOVAs did not reveal significant interaction effects (group x fasting) or group differences in adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), phosphodiesters (PDE), or pH levels between MDD and CTRL. Fasting, independent of group, significantly increased ATP and decreased Pi levels and an overall increase in PME/PDE ratio as marker for membrane turnover was observed. Overall these results indicate reactive changes in cerebral energetics and in membrane phospholipid metabolism in response to fasting. The observed effects did not significantly differ between CTRL and MDD, indicating that neurometabolic adaptation to metabolic stress is preserved in MDD patients.

Methionine overcomes neural tube defects in rat embryos cultured on sera from laminin-immunized monkeys.

Sera from laminin-immunized monkeys were previously found to cause neural tube defects in cultures of whole rat embryos by unknown mechanisms. In the present study, adding L-methionine to either the culture media or to the diets of the monkeys overcame the toxicity of the serum from one of these monkeys (LAM3) but not the other (LAM4). The antilaminin antibody levels and avidities for isolated murine laminin of sera from the two monkeys were comparable. However, when yolk sac homogenates were tested on ELISA, antibodies from LAM4 had greater binding than LAM3, which was further supported by immunoelectron microscopy. These differences in antibody binding were explained by the findings that antibodies from LAM4 recognized more epitopes than LAM3 and that LAM4 recognized specific epitopes not recognized by LAM3. These antibodies caused reductions in the number of microvilli on the cells and the cell sizes of the yolk sac endoderm. In addition, uptake of [14C]methionine, [14C]sucrose and [14C]valine by yolk sacs from embryos cultured on serum from LAM4 was less than that for LAM3. We suggest that the neural tube defects caused by the antilaminin antibodies were a result of reduced nutrient flow caused by the reduction in the number of microvilli on the cells of the yolk sac endoderm.

Methionine decreases the embryotoxicity of sodium valproate in the rat: in vivo and in vitro observations.

Methionine provided in the drinking water of pregnant rats injected with sodium valproate reduced the frequency of resorptions but did not improve embryo growth. Rats drinking methionine supplemented water had approximately twice the level of serum-free methionine and consumed only one-half the volume of water of controls. Using whole rat embryo cultures, the simultaneous addition of methionine and sodium valproate to the medium provided no protection from neural tube defects, nor did the addition of methionine to a medium of serum obtained from rats previously dosed with sodium valproate. However, protection from the teratogenic effects of sodium valproate was afforded by methionine when the culture medium was sera from rats consuming methionine and was particularly striking when embryos for culture were taken from pregnant rats that had been consuming methionine. These observations along with those of others indicated the importance of dietary and culture media methionine levels in evaluating experimental and regulatory teratology studies and suggested the possibility that methionine may play an important role in human teratology where multifactorial causes have been implicated in problems such as neural tube closure defects.