Abstract
Background: Maternal overnutrition critically influences offspring's long-term metabolic and cognitive health. While prior research indicates maternal diet can disrupt hippocampal function, the specific impact on spatial memory remains unclear. Methods: Female mice were fed a high-fat diet (HFD) for nine weeks before and during pregnancy. Offspring were weaned onto a standard diet and tested at postnatal day 90 using the dry maze, a spatial reference memory task. Results: HFD-exposed offspring exhibited significant learning acquisition impairments, with prolonged latencies in locating hidden rewards and diminished within-session improvements compared to controls. During the probe trial, they spent significantly less time in the target quadrant, indicating long-term spatial memory retention deficits. Notably, these cognitive impairments occurred independently of body weight differences at testing. Discussion: This study uniquely demonstrates that maternal HFD exposure induces specific spatial memory deficits in adult offspring, potentially through neurodevelopmental alterations preceding metabolic dysfunction. The results highlight the importance of prenatal nutrition in shaping cognitive outcomes later in life. Conclusions: These findings extend our understanding of how prenatal nutrition impacts cognitive aging and disease susceptibility. Given rising obesity rates among women of reproductive age, this research underscores the urgent need for targeted interventions to mitigate the intergenerational effects of maternal overnutrition on brain function.