Elevated levels of methionine in blood characterize the hypermethioninemia, which may have genetic or non‐genetic origin, as for example from high protein diet. Born rats from hypermethioninemic mothers presented cerebral oxidative stress, inhibition of Na+,K+‐ATPase, memory deficit and ultrastructure cerebral changes. Melatonin is a hormone involved in circadian rhythm and has antioxidant effects. The aim of this study was to verify the possible neuroprotective effects of melatonin administration in hypermethioninemic pregnant rats on damage to biomolecules (Na+,K+‐ATPase, sulfhydryl content and DNA damage index) and behavior (open field, novel object recognition and water maze tasks), as well as its effect on cells morphology by electron microscopy in offspring. Wistar female rats received methionine (2.68 μmol/g body weight) and/or melatonin (10 mg/kg body weight) by subcutaneous injections during entire pregnancy. Control rats received saline. Biochemical analyzes were performed at 21 and 30 days of life of offspring and behavioral analyzes were performed only at 30 days of age in male pups. Results showed that gestational hypermethioninemia diminished Na+,K+‐ATPase activity and sulfhydryl content and increased DNA damage at 21 and 30 days of life. Melatonin was able to totally prevent Na+,K+‐ATPase activity alteration at 21 days and partially prevent its alteration at 30 days of rats life. Melatonin was unable in to prevent sulfhydryl and DNA damage at two ages. It also improved DNA damage, but not at level of saline animals (controls). Regarding to behavioral tests, data showed that pups exposed to gestational hypermethioninemia decreased reference memory in water maze, spent more time to the center of the open field and did not differentiate the objects in the recognition test. Melatonin was able to prevent the deficit in novel object recognition task. Electron microscopy revealed ultrastructure alterations in neurons of hypermethioninemic at both ages of offspring, whose were prevented by melatonin. These findings suggest that melatonin may be a good neuroprotective to minimize the harmful effects of gestational hypermethioninemia on offspring.

中文翻译：

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褪黑激素在妊娠期高甲硫氨酸血症模型中的神经保护作用

血液中蛋氨酸水平升高是高蛋氨酸血症的特征，这可能具有遗传或非遗传起源，例如来自高蛋白饮食。高甲硫氨酸母鼠出生的大鼠出现脑氧化应激、Na+、K+-ATP 酶抑制、记忆力减退和脑超微结构改变。褪黑激素是一种参与昼夜节律的激素，具有抗氧化作用。本研究的目的是验证褪黑激素在高甲硫氨酸血症妊娠大鼠中对生物分子损伤（Na+、K+-ATPase、巯基含量和 DNA 损伤指数）和行为（开放领域、新物体识别和水迷宫任务）可能的神经保护作用。 )，以及其对后代细胞形态的电子显微镜检查。Wistar 雌性大鼠接受甲硫氨酸 (2. 68 μmol/g 体重）和/或褪黑激素（10 mg/kg 体重），在整个怀孕期间皮下注射。对照大鼠接受盐水。生化分析在后代出生 21 天和 30 天时进行，而行为分析仅在雄性幼崽 30 天大时进行。结果表明，妊娠期高甲硫氨酸血症会降低 Na+、K+-ATP 酶活性和巯基含量，并增加 21 天和 30 天的 DNA 损伤。褪黑激素能够在 21 天完全阻止 Na+,K+-ATPase 活性改变，并在大鼠生命 30 天时部分阻止其改变。褪黑激素在两个年龄段都无法防止巯基和 DNA 损伤。它还改善了 DNA 损伤，但不是在盐水动物（对照）水平上。关于行为测试，数据显示，暴露于妊娠期高甲硫氨酸血症的幼崽会降低水迷宫中的参考记忆，花更多时间在开阔场地的中心，并且在识别测试中无法区分物体。褪黑激素能够防止新物体识别任务中的缺陷。电子显微镜显示子代两个年龄段高甲硫氨酸血症神经元的超微结构改变，褪黑激素可以阻止这些改变。这些发现表明，褪黑激素可能是一种很好的神经保护剂，可以最大限度地减少妊娠期高甲硫氨酸血症对后代的有害影响。电子显微镜显示子代两个年龄段高甲硫氨酸血症神经元的超微结构改变，褪黑激素可以阻止这些改变。这些发现表明，褪黑激素可能是一种很好的神经保护剂，可以最大限度地减少妊娠期高甲硫氨酸血症对后代的有害影响。电子显微镜显示子代两个年龄段高甲硫氨酸血症神经元的超微结构改变，褪黑激素可以阻止这些改变。这些发现表明，褪黑激素可能是一种很好的神经保护剂，可以最大限度地减少妊娠期高甲硫氨酸血症对后代的有害影响。