Indomethacin attenuates neuroinflammation and memory impairment in an STZ-induced model of Alzheimer's like disease

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) exposure might be considerably associated with a decreased risk of Alzheimer's disease (AD). Therefore, we conducted an experiment to investigate the impact of indomethacin (IND) on inflammasome as a key player of neuroinflammation. Methods: The Alzheimer's-like condition was induced by streptozotocin (STZ) in rats. IND was injected intraperitoneally 1 d prior to STZ administration and resumed with 2 d interval up to 60 d. Morris water maze (MWM) was utilized to assess learning and memory. The expression level of genes that contribute to the inflammasome pathway was measured using real-time polymerase chain reaction (PCR). To authenticate the obtained outcomes, immunostaining for caspase-1, interleukin-1 beta (IL-1 beta), and phosphorylated tau (p-Tau) protein was conducted. Results: Behavioral experiments indicated that IND treatment was able to improve learning and memory performance (p<.05). A significant decrease in C-terminal caspase recruitment domain [CARD] domain-containing protein 4 (NLRC4), nucleotide-binding oligomerization domain [NOD]-like receptor protein 3 (NLRP3), IL-1 beta, and apoptosis-associated speck-like protein containing CARD (ASC) mRNA expression was recorded in IND administered group compared with the STZ group (p<.05). Furthermore, expression levels of IL-18 and caspase-1 in the hippocampus of IND-treated group tended to decrease. Immunostaining evaluations showed that few positive cells for caspase-1, IL-1 beta, and p-Tau protein in IND treated animals, whereas the number of positive cells was considerably increased in STZ treated animals (p<.05). Conclusion: It could be deduced that IND improves neuroinflammation and memory impairment in AD through decreasing IL-1 beta and caspase-1 that are associated with suppression of NLRC4 and NLRP3 inflammasome genes. This holds the potential to introduce valuable targets in the field for successful combat against AD.