Development of an animal model for gestational hypermethioninemia in rat and its effect on brain Na+,K+-ATPase/Mg2+-ATPase activity and oxidative status of the offspring

In the present study we developed a chemically induced experimental model for gestational hypermethioninemia in rats and evaluated in the offspring the activities of Na+,K+-ATPase and Mg2+-ATPase, as well as oxidative stress parameters, namely sulfhydryl content, thiobarbituric acid-reactive substances and the antioxidant enzymes superoxide dismutase and catalase in encephalon. Serum and encephalon levels of methionine and total homocysteine were also evaluated in mother rats and in the offspring. Pregnant Wistar rats received two daily subcutaneous injections of methionine throughout the gestational period (21 days). During the treatment, a group of pregnant rats received dose 1 (1.34 μmol methionine/g body weight) and the other one received dose 2 (2.68 μmol methionine/g body weight). Control group received saline. After the rats give birth, a first group of pups was killed at the 7th day of life and the second group at the 21th day of life for removal of serum and encephalon. Mother rats were killed at the 21th day postpartum for removal of serum and encephalon. Both doses 1 and 2 increased methionine levels in encephalon of the mother rats and dose 2 increased methionine levels in encephalon of the offspring. Maternal hypermethioninemia also decreased the activities of Na+,K+-ATPase, Mg2+-ATPase and catalase, as well as reduced total sulfhydryl content in the encephalon of the pups. This chemical model seems to be appropriate for studies aiming to investigate the effect of maternal hypermethioninemia on the developing brain during gestation in order to clarify possible neurochemical changes in the offspring.