Diseases with peripheral inflammation, such as sepsis and peritonitis, are associated with an increased risk of central nervous system diseases. Injection of lipopolysaccharide (LPS) into mice has been widely used as a disease model for peripheral inflammation and exhibit cognitive dysfunction. Although glial cells have been implicated in the pathogenesis of cognitive dysfunction, the detailed mechanisms remain unclear, and most studies have been conducted in young or old mice. In this study, we examined the effects of LPS on short-term memory in adult mice to elucidate the mechanisms of pathogenesis.
C57BL/6N mice (male, 11-13 weeks old) were injected with LPS (3 mg/kg, i.p.). At 7 days after injection, the novel object recognition test was conducted, and LPS decreased the discrimination index. At 7 days after injection, the number of c-Fos+ cells, a marker of neuronal activation, decreased in the hippocampal CA1 region, and the percentage of immature spines detected by Golgi-Cox staining was increased. The gene expression of several inflammatory factors peaked at 1-3 days after LPS injection and recovered to pre-injection levels at 7 days after injection.
These results indicate that the short-term memory impairment was observed at 7 days after LPS injection. Inhibition of hippocampal CA1 neuron activation and the decrease in synaptic strength due to immature spines may be involved in the short-term memory impairment.