Late pregnancy maternal naringin supplementation affects the mitochondria in the cerebellum of Wistar rat offspring via sirtuin 3 and AKT.

Dietary polyphenol consumption is associated with a wide range of neuroprotective effects by improving mitochondrial function and signaling. Consequently, the use of polyphenol supplementation has been investigated as an approach to prevent neurodevelopmental diseases during gestation; however, the data obtained are still very inconclusive, mostly because of the difficulty of choosing the correct doses and period of administration to properly prevent neurodegenerative diseases without undermining normal brain development. Thus, we aimed to evaluate the effect of naringin supplementation during the third week of gestation on mitochondrial health and signaling in the cerebellum of 21-day-old offspring. The offspring born to naringin-supplemented dams displayed higher mitochondrial mass, membrane potential, and superoxide content in the cerebellum without protein oxidative damage. Such alterations were associated with dynamin-related protein 1 (DRP1) and phosphorylated AKT (p-AKT) downregulation, whereas the sirtuin 3 (SIRT3) levels were strongly upregulated. Our findings suggest that high dietary polyphenol supplementation during gestation may reduce mitochondrial fission and affect mitochondrial dynamics even 3 weeks after delivery via SIRT3 and p-AKT. Although the offspring born to naringin dams did not present neurobehavioral defects, the mitochondrial alterations elicited by naringin may potentially interfere during neurodevelopment and need to be further investigated.

Naringin Supplementation during Pregnancy Induces Sex and Region-Specific Alterations in the Offspring's Brain Redox Status.

Research has shown the beneficial effects of naringin supplementation to adult rodents, which can ameliorate oxidative stress in disease models. However, evidence has demonstrated that polyphenol supplementation induced detrimental effects when consumed during sensitive periods of development, such as pregnancy. Therefore, we investigated the effect of maternal naringin supplementation during pregnancy on the offspring's cerebral redox status. Pregnant Wistar rats were divided into control and naringin groups and supplemented from gestational day 15 to gestational day 21. On postnatal days 1, 7, and 21, offspring were euthanized, and the prefrontal cortex, hippocampus, striatum, and cerebellum dissected. On postnatal day 1, maternal naringin supplementation positively modulated the pups' brain redox status. On postnatal day 7, a pro-oxidative milieu was observed in the offspring's striatum and cerebellum in a sex-dependent manner, even though the prefrontal cortex and hippocampus were not negatively affected. Besides, the alterations observed on postnatal day 7 did not persist up to weaning. Our findings demonstrated that the effect induced by naringin supplementation in the brain redox status differed according to the period of development in which naringin was consumed since the beneficial effects usually found in the adult rodents became detrimental when the supplementation was applied during pregnancy.

Adaptive effects of gestational caloric restriction in the mitochondria of Wistar rats' brain: A DOHaD approach.

Developmental origins of health and disease (DOHaD) is a field of biological science dedicated to investigating how different interventions during development affect an individual's life. Diet is an essential way to interact with the environment, and during pregnancy affects not only the mother but also can impact the next generations. One of these interventions is caloric restriction (CR), which has shown positive redox modulation in rats' offspring when malnutrition is responsibly controlled. Considering that mitochondrial metabolism is determinant for redox status, we investigated parameters related to mitochondrial functionality and reactive species levels in offspring's brain from rats delivered to pregnant caloric restricted dams. Therefore, pregnant rats were divided between control (ad libitum food) and CR (20% food restriction plus micronutrients supplementation) groups, and offspring's brain was analyzed on post-natal days (PND) 0, 7, 21, and 60. Mitochondrial function, as well as superoxide content, were decreased in most brain areas on PND0 and went through adaptation, showing increased mass and membrane potential in adulthood. Concerning mitochondrial electron transport system (METS), the most affected area was the cerebellum, which was impaired at birth and activated at adulthood. In conclusion, our results show that gestational CR promotes adaptation from impaired mitochondrial parameters at birth, improving mitochondrial function when compared to control, without increasing superoxide generation, at adult age. More studies are necessary in order to support the use of CR as a clinical approach.