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

Abstract

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.