Chronic Neuroinflammation Induced by Systemic Administration of Lipopolysaccharide Leads to Behavioral Impairments in Mice

Abstract

Background: There is evidence that chronic neuroinflammation is involved in the pathogenesis of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. In this regard, animal models are considered important tools for the study of neuroinflammation associated with these diseases. The injection of lipopolysaccharide (LPS) is the most commonly used approach for inducing neuroinflammation in animal models. However, there are limited and inconsistent studies regarding the effect of the chronic administration of LPS on behavioral parameters. Accordingly, this experimental study aimed to compare the effect of the chronic injection of LPS in two different doses on behavioral alterations, including spatial learning and working memory in mice. Methods: Thirty-six male BALB/c mice were used in this study. After acclimatization for a week, mice were randomly divided into three groups. Control mice were intraperitoneally (IP) injected with saline for seven consecutive days, and mice of the second group received 250 μg/kg LPS (IP) dissolved in saline for a week. Finally, mice of the third group were administered 750 μg/kg LPS (IP) dissolved in saline for a week. Morris water maze (MWM) and Y-maze were performed to assess spatial learning and working memory alterations in treated mice, respectively. Results: It was found that LPS treatment with a high dose (750 μg/kg) results in working memory impairment (P=0.0024) and cognitive dysfunction (P=0.0030) based on Y-maze and MWM test results. Conclusion: Our findings suggest that the LPS-induced model of chronic neuroinflammation can be used as an important tool for the investigation of the pathomechanisms of neurodegenerative disorders and the development of new pharmacotherapeutic options.