Effects of Different Lipopolysaccharide Doses on Short- and Long-Term Spatial Memory and Hippocampus Morphology in an Experimental Alzheimer’s Disease Model

Abstract

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. Various animal models are widely used to investigate its underlying mechanisms, including lipopolysaccharide (LPS)-induced neuroinflammation models. Aim: In this study, we aimed to investigate the effect of different doses (0.25, 0.5, and 0.75 mg/kg) of LPS on short- and long-term spatial memory and hippocampal morphology in an experimental AD mouse model. Materials and methods: Twenty-four adult male Swiss mice (SWR/J) weighing 18–25 g were divided into four groups: control, 0.25 mg/kg LPS, 0.50 mg/kg LPS, and 0.75 mg/kg LPS. All groups were treated with LPS or vehicle for 7 days. Behavioral tests were started (Morris water maze for 6 days and Y maze for 1 day) on the last 2 days of injections. After the behavioral procedures, tissues were collected for further histological investigations. Result: All LPS doses induced significant short- and long-term spatial memory impairment in both the Y maze and Morris water maze compared with the control group. Furthermore, histological examination of the hippocampus indicated degenerating neurons in both the 0.50 mg/kg and 0.75 mg/kg LPS groups, while the 0.25 mg/kg LPS group showed less degeneration. Conclusion: our results showed that 0.75 mg/kg LPS had a greater impact on early-stage spatial learning memory and short-term memory than other doses. Our behavioral and histological findings suggest 0.75 mg/kg LPS as a promising dose for LPS-induced AD models.

Keywords

• neuroinflammation
• reference memory
• working memory
• Morris water maze