Obesity is a low-grade inflammatory state and a fetus developing in such an inflammatory milieu is susceptible to developing various disorders. After birth, children of obese mothers are at increased risk of obesity, metabolic syndrome and neurodevelopmental abnormalities, eg reduced cognitive capacity, developmental delay, attention deficit hyperactivity disorder schizophrenia, and autism spectrum disorders. Here we used rats to test the effects of maternal obesity on neuronal networking and to determine if establishing a good diet at weaning could rescue deficits.
Rats gestated and maintained on an obesogenic Western diet (WD) had impaired spatial and working memory compared with rats on control chow (CC) at 10 weeks of age. Switching to CC when 3 weeks old completely rescued working memory but had no effect on spatial memory. Brain slices from 15 week old WD male rats had hippocampal epileptiform activity, which reflected current diet. This was supported by epileptiform spike-wave bursts, associated with a “freezing” of movement (absence), in EEG recordings in conscious free-moving animals. Immunohistochemistry revealed a marked reduction in GABA staining, with a reduction in NPY and somatostatin neurons reflecting current diet and somatostatin neurons also very much reduced in rats exposed to WD during gestation and weaning.
Activators of NPY receptors suppress spike-wave activity in absence epilepsies in humans and animal models and the reduction in NPY and occurrence of epileptiform activity in our WD rats supports these observations. A 2017 study of 1.4 million children from Sweden found that the incidence of childhood epilepsy increased with maternal BMI during pregnancy. Our results provide some insights into interpretation of this. Abnormal network and epileptiform activity has been associated with the early stages of Alzheimer’s disease. It is alarming to consider that exposure to WD effects as early as in utero might predispose to earlier AD.