Investigation of inflammasome activation in neonatal brain born to HİGH-FAT dieted dams

Aim : Different inflammatory pathways in the body trigger inflammation. One of them is the activation of NLRP3 inflammasome. Although it has been shown that NLRP3 inflammasome is activated in different tissues as a result of feeding with a high-fat diet; it is not known whether feeding the dam with a high-fat diet during pregnancy and lactation triggers NLRP3 inflammasome activation in the offspring's brain. In our study, we aimed to demonstrate the activation of NLRP3 inflammasome in offsprings' brains born from mice fed a high-fat diet with different fatty acid composition. Method: Our study consists of 5 groups. Dams were fed with their own feed groups until 3 weeks before mating. Female mice in 2 groups were fed with standard control chow; female mice in the other 3 groups were fed a high-fat diet in which 50% of the energy from the diet came from fat. A group of mouse pups born from dams fed a control diet were injected with LPS, which is known to activate NLRP3 inflammasome on days PN4-6, as a positive control. For each group, a total of 20 female mice, including 4 females of the C57BL/6 type, and for each group born from these dams, a total of 70 mouse pups were studied, 7 on PN7 day and 7 on PN28 day. Results: When the sacrified pups brains were evaluated, it was found that both hippocampus and prefrontal cortex neuron density decreased in the pups in the LPS injection group on the 7th and 28th days; NLRP3 inflammasome activation was observed. In both PN7 and PN28, neuron density seems to be affected especially in the SFA-HFD group. In PN7, while NLRP3 activation in the prefrontal cortex was not significant in high-fat diet groups; microglial activation was evident. On the other hand, NLRP3 inflammasome activation was evident in the hippocampus in PN7, especially for the SFA-HFD group. For PN28, NLRP3 inflammasome activation and microglial activation were evident in both the prefrontal cortex and hippocampus in both the SFA-HFD and O6/O3:20/1-HFD groups. The high Omega-3 level in the O6/O3:2/1-HFD group had a decreasing effect on inflammasome activation. Conclusion : Feeding dams with a high-fat diet during pregnancy and lactation causes microglial and NLRP3 inflammasome activation in the brain. Keywords: Neuroinflammation, microglia, NLRP3, newborn, hippocampus, prefrontal cortex