Maternal overnutrition leads to cognitive and neurochemical abnormalities in C57BL/6 mice.

Epidemiological studies have linked maternal obesity with metabolic as well as psychiatric disorders in the progeny. However, very little is known how maternal overnutrition may affect the cognitive abilities of the offspring. Here, we tested the hypothesis whether maternal high-fat diet (HFD) exposure in mice may induce long-term cognitive impairments and neurochemical dysfunctions in the offspring during different age trajectories. We found that maternal HFD led to cognitive disabilities in adult offspring compared to controls. It was mostly evident in a reference memory and in an associative learning paradigm. More severe and pervasive impairments were evident in the aged adult group across multiple cognitive domains. In addition, adult and aged adult HFD offspring showed potentiation of prepulse inhibition. The cognitive impairments observed at adulthood were associated with attenuations of amino acid levels in the medial prefrontal cortex and the hippocampus regions. Our results suggest that HFD offspring are at an increased risk to develop cognitive deficits, affecting learning and memory processes in adulthood. Furthermore, maternal HFD exposure may facilitate or even drive pathological brain aging mainly in the hippocampal and prefrontal cortex structures that may explain the cognitive deficits observed in the offspring.