Roles of Lcn2 and neuroinflammation in a scopolamine-induced cognitive impairment animal model: implication of the NLRP3 inflammasome pathway

Abstract

Background: With increasing life expectancy in modern society, the prevalence of age-related diseases has risen, among which cognitive impairment represents a major health challenge. Lipocalin-2 (Lcn2) and neuroinflammation have recently emerged as important contributors to cognitive dysfunction. Objective: This study aimed to investigate the relationship between Lcn2-associated neuroinflammation and cognitive impairment using a scopolamine (SCO)-induced mouse model. Methods: Behavioral performance was assessed using the Y-maze and novel object recognition test (NORT). Hippocampal mRNA expression levels of Lcn2 and inflammatory factors were analyzed by quantitative real-time PCR. In addition, the anti-inflammatory drug diclofenac (DIC) was administered to evaluate its effects on neuroinflammation and cognitive function. Results: SCO administration impaired behavioral performance and increased the expression of Lcn2, multiple inflammatory markers, and NLRP3 inflammasome–related components. DIC treatment improved behavioral outcomes and reduced the expression of several of these inflammatory factors. Conclusions: These findings suggest that Lcn2-associated neuroinflammation, potentially involving the NLRP3 inflammasome pathway, contributes to SCO-induced cognitive impairment. Dic may alleviate these changes by suppressing inflammatory signaling.