Cognition, Behavior, and Memory
Author: Sofía Quiroga | Email: email@example.com
Sofía Quiroga 1°, María Agustina Vidal 1°, Adriana Laura Burgueño 1°, Ana María Genaro 1°
1° Instituto de Investigaciones Biomédicas (BIOMED) CONICET-UCA
Previously, we showed that chronic stress (CS) and/or high-fat diets (HFD) promote cognitive impairment. We compared the effect of HFD and/or CS in C57Bl/6J
(WT) and TLR4 KO male mice to analyze the role of NLRP3 inflammasome in cognitive impairment. For 12 weeks, starting at 4 weeks of age, mice were fed a standard diet (SD) or HFD. Then, they were exposed (or not) to CS for 8 weeks. We conducted the Object location test (OLT) and Barnes Maze (BM) to assess cognitive performance. Our results showed that HFD or CS decreased the discrimination index (DI) in OLT, while in KO only CS altered it. In WT, CS and HFD decreased the time in the target quadrant (TTQ) in BM. Regardless of the treatment, KO mice showed higher DI in OLT, spent more TTQ, and made fewer reference and working errors in BM, showing better spatial learning and memory than WT. Hippocampal mRNA expression levels of NLRP3 inflammasome components were assessed by qPCR. In WT mice, HFD or CS upregulated NLRP3 and PYCARD mRNA expression, suggesting an inflammatory process in the hippocampus of these animals. In contrast, KO mice showed lower expression of PYCARD, IL18 and caspase-1 possibly implying decreased NLRP3 inflammasome activity. These results suggest the involvement of TLR4 in the development of cognitive deficits in WT mice in response to HFD and/or CS. Further analysis of protein expression will be necessary for a better understanding of the role of TLR4 in this animal model.