Gestational exposure to a ketogenic diet increases sociability in CD-1 mice

Postnatal administration of high-fat, low-carbohydrate ketogenic diets (KDs) is an established and effective treatment option for refractory epilepsy, with more recently identified therapeutic potential across a wide range of preclinical models of neurological and psychiatric disorders. However, the impact of gestational exposure to a KD (GKD) on offspring development remains unclear. Previous work has found that GKD exposure reduces depression- and anxiety-like behaviors in CD-1 mice, whereas postnatal KD improves sociability in several different rodent models of autism. Here we examined how sociability is impacted by GKD. Given that the neuropeptide oxytocin positively regulates affect, anxiety, and sociability, we also examined the effects of GKD on brain oxytocin expression. Male and female CD-1 mice exposed to either a standard diet (SD) or a KD gestationally were cross-fostered with SD dams at birth and remained on a SD from that point onward. These offspring were then tested for sociability and social novelty (three-chambered test) and depressive-like behaviors (forced swim test) at 10 weeks of age. At the conclusion of testing, brain tissue was collected and immunohistochemically processed for oxytocin expression in hypothalamic and limbic areas. We found that GKD increased sociability and reduced depressive-like symptoms, without affecting oxytocin expression in quantified areas. By expanding the scope of the lasting impact of gestational exposure to a ketogenic diet to include positive effects on sociability, these results indicate that GKDs may have novel therapeutic applications for individuals at risk for developmental disorders of social behavior, including autism and schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).