Gestational caloric restriction improves redox homeostasis parameters in the brain of Wistar rats: a screening from birth to adulthood

Abstract Caloric restriction (CR) improves health and life span in animal models. Although CR effects in adult life are well described, little is known about effects on offspring when applied during gestation. Pregnancy is a remarkable period of life, alterations in this stage lead to lifelong consequences, some of which, associated to redox unbalance. Furthermore, gestational overweight is a growing issue that can lead to detrimental outcomes. To address this issue, we divided pregnant rats into control (ad libitum food) and CR groups, which received 20% less food than control. Micronutrients consumption was equalized between groups by oral gavage. Cerebellum, prefrontal cortex, hippocampus, and hypothalamus were evaluated on post-natal day (PND) 0, 7, 21, and 60. We observed increased oxidants content on PND0 in all brain structures, except for the cerebellum. Key enzymatic antioxidant defenses showed decreased activity on PND0. Interestingly, on PND60, we observed a positive modulation of most antioxidant enzymes, especially on the prefrontal cortex and hippocampus. Non-enzymatic antioxidant defenses were decreased at birth and increased during development and adult age. Lipid peroxidation was increased at birth on most structures, and the effect was abolished thereafter. In the prefrontal cortex, lipid peroxidation was unaltered at birth and diminished thereafter, while protein oxidation was increased on PND0 and decreased on PND60. Protein oxidation was also decreased in the cerebellum at adult age. Our results shown controlled gestational CR to improve antioxidant defenses and protect offspring's brain from oxidative stress, especially in adulthood, as a result of developmental metabolic programming.