Environmental enrichment alters neurobehavioral development following maternal immune activation in mice offspring with epilepsy

Epilepsy is a chronic brain disease affecting millions of people worldwide. Anxiety-related disorders and cognitive deficits are common in patients with epilepsy. Previous studies have shown that maternal infection/ immune activation renders children more vulnerable to neurological disorders later in life. Environmental enrichment has been suggested to improve seizures, anxiety, and cognitive impairment in animal models. The present study aimed to explore the effects of environmental enrichment on seizure scores, anxiety-like behavior, and cognitive deficits following maternal immune activation in offspring with epilepsy. Pregnant mice were treated with lipopolysaccharides-(LPS) or vehicle, and offspring were housed in normal or enriched environments during early adolescence to adulthood. To induce epilepsy, adult male and female offspring were treated with Pentylenetetrazol-(PTZ), and then anxiety-like behavior and cognitive functions were assessed. Tumor necrosis-factor (TNF)-alpha and interleukin (IL) 10 were measured in the hippocampus of offspring. Maternal immune activation sex-dependently increased seizure scores in PTZ-treated offspring. Significant increases in anxiety-like behavior, cognitive impairment, and hippocampal TNF-alpha and IL-10 were also found following maternal immune activation in PTZ-treated offspring. However, there was no sex difference in these behavioral abnormalities in offspring. Environmental enrichment reversed the effects of maternal immune activation on behavioral and inflammatory parameters in PTZ-treated offspring. Overall, the present findings highlight the adverse effects of prenatal maternal immune activation on seizure susceptibility and psychiatric comorbidities in offspring. This study suggests that environmental enrichment may be used as a potential treatment approach for behavioral abnormalities following maternal immune activation in PTZ-treated offspring.

Automated summary

Maternal immune activation can increase seizure susceptibility and psychiatric comorbidities in offspring, leading to anxiety and cognitive deficits with impact on inflammatory parameters, without sex differences in offspring. Environmental enrichment is shown to reverse these effects and can be considered as a potential treatment approach for behavioral abnormalities following maternal immune activation in offspring with epilepsy.