Characterization of Parental Ketogenic Diet Effects on the Neurodevelopment of Wistar Rats

Abstract

Introduction: Advanced maternal age (AMA) is increasingly common and associated with a higher risk of neurodevelopmental disorders in offspring. Maternal nutrition is a key factor in fetal brain development, influencing cognitive and behavioral outcomes. The ketogenic diet (KD), a high-fat, low-carbohydrate regimen, has demonstrated neuroprotective properties, but its effects on fetal neurodevelopment remain unclear. This study explores the impact of maternal KD before and during pregnancy on neurodevelopmental and behavioral outcomes in offspring of AMA pregnancies. Methods: Wistar Han rats were used as progenitors and were assigned via cluster randomization to either a control diet (CD) or a ketogenic diet (KD), with dietary intervention starting at 3 months of age. Offspring were studied from postnatal day 1 to 21, with assessments including neurodevelopmental milestones and somatic parameters. Reflexes such as Surface Righting, Negative Geotaxis, Cliff Aversion, Forelimb Grasp, and Locomotor Activity were evaluated. Reflex acquisition was assessed based on response latency and time to emergence. Somatic parameters, including Body Weight, Eye Opening, and Fur Development, were recorded daily. Results: Both litters from the CD and KD groups increased their weight during the experimental time (F = 173.07, p < 0.0001). However, CD litters gained more weight than the KD litters during this period (F = 17.50, p < 0.0058). Maternal KD did not significantly affect most neurodevelopmental reflexes. Nevertheless, KD pups exhibited reduced locomotor response latency on P9 (β = -4.100, P = 0.04) and P10 (β = -6.050, P = 0.03), suggesting potential diet-related modulation of motor function. Conclusion: While maternal KD did not delay neurodevelopmental milestones, it may subtly influence motor function by altering locomotor response latency. These findings suggest that early-life ketosis may modulate neural excitability and motor coordination. However, given the limited sample size, further research is needed to determine the long-term implications of maternal KD in AMA pregnancies.