Impact of Maternal Ketogenic Diet on NLRP3 Inflammasome Response in the Offspring Brain

Abstract

The effects of maternal diet on the neuroimmune responses of the offspring remain to be elucidated. We investigated the impact of maternal ketogenic diet (KD) on the NLRP3 inflammasome response in the offspring’s brain. C57BL/6 female mice were randomly allocated into standard diet (SD) and ketogenic diet (KD) groups for 30 days. After mating, the presence of sperm in the vaginal smear was considered day 0 of pregnancy, and female mice continued their respective diets during pregnancy and the lactation period. Following birth, pups were further allocated into two groups and given either LPS or intraperitoneal saline on postnatal (PN) days 4, 5 and 6; they were sacrificed on PN11 or PN21. Neuronal densities were significantly lower globally in the KD group when compared to the SD group at PN11. Neuronal density in the prefrontal cortex (PFC) and dentate gyrus (DG) regions were also significantly lower in the KD group when compared to the SD group at PN21. Following administration of LPS, the decrease in the neuronal count was more prominent in the SD group when compared to the KD group in the PFC and DG regions at PN11 and PN21. NLRP3 and IL-1β were higher in the KD group than in the SD group at PN21 in the PFC, CA1 and DG regions, and were significantly lower in the DG region of the KD group especially when compared to the SD group following LPS. Results of our study reveal that maternal KD negatively affects the offspring’s brain in the mouse model. The effects of KD exhibited regional variations. On the other hand, in the presence of KD exposure, NLRP3 expression after LPS injection was lower in the DG and CA1 areas but not in the PFC when compared to SD group. Further experimental and clinical studies are warranted to elucidate the molecular mechanisms underlying the impact of antenatal KD exposure and regional discrepancies on the developing brain.