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

Abstract

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 Mg(2+)-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, Mg(2+)-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.

Gestational hypermethioninaemia alters oxidative/nitrative status in skeletal muscle and biomarkers of muscular injury and inflammation in serum of rat offspring

“…We chose to carry out the analysis on day 21 after birth because in our previous work we investigated the effects of maternal hypermethioninaemia on 7‐ and 21‐day‐old pups and only the latter pups showed alterations in the parameters evaluated (Schweinberger et al . ). As the placenta exerts a maternal–foetal transfer of anti‐oxidants during gestation, we believe that younger pups have anti‐oxidant protection provided by their mothers.…”

“…In agreement with these results, we have previously shown that Met treatment during pregnancy reduces sulfhydryl content in brain of rat pups (Schweinberger et al . ). In addition, Stefanello et al .…”

“…In agreement, we have previously reported, with the same animal model, that maternal hypermethioninaemia reduces CAT activity in encephalon of pups (Schweinberger et al . ).…”

“…As we have recently developed an experimental model of gestational hypermethioninaemia, which induces oxidative stress in encephalon of rat offspring (Schweinberger et al . ) and this oxidative stress is correlated with sarcopaenia and other muscle diseases (Tidball & Wehling‐Henricks ; Arbogast et al . ; Turki et al .…”

Prenatal hyperhomocysteinemia induces oxidative stress and accelerates ‘aging’ of mammalian neuromuscular synapses

“…hHCY is often followed by skeletal muscle dysfunctions, evidenced by muscle weakness, less fatigue resistance due to oxidative stress, inflammation and endoplasmic reticulum stress in mice (Swart et al, 2013; Schweinberger et al, 2014; Veeranki and Tyagi, 2015; Majumder et al, 2017, 2018a,b). The elevated levels of HCY are associated with neurodegenerative disorders and amyotrophic lateral sclerosis (ALS) (McCully, 2017; Sharma et al, 2015; Swart et al, 2013).…”