Effects of immune system activation on learning and memory in rodent models of Alzheimer's pathogenesis.

摘要

Experimental evidence from molecular biology, biochemistry, epidemiology and behavioral pharmacology support the conclusion that brain inflammation contributes to the pathogenesis of cognitive disorders in Alzheimer's disease and other neuropsychological disorders. Five experiments were conducted to determine whether biological events associated with acute systemic inflammation are sufficient to cause learning and working memory deficits in rats. These experiments utilized the non-specific immunostimulant, lipopolysaccharide (LPS), to induce an immune response in rats, and the effects of LPS on performance of behavioral tasks designed to measure, in separate experiments, spatial or symbolic working memory, spatial learning acquisition, and spatial memory consolidation, was evaluated. A sixth experiment utilized a transgenic-mouse model of Alzheimer's disease APPSW Tg mice), characterized by constitutive, age-dependent development of chronic neuroinflammation and cognitive dysfunction. APPSW Tg mice were treated with non-steroidal anti-inflammatory drugs and the effects on performance in a learning and memory task on which untreated APPSW Tg mice have been reported to be impaired, was evaluated. Immune mechanisms were found not to affect learning or memory processes in any of the behavioral measures used. However, LPS-induced immune activation caused performance deficits consistent with a disruptive effect of LPS on motivation and arousal. These results suggest that acute immune activation is not sufficient to produce Alzheimer's-like cognitive dysfunction in animals, and that sickness behavior induced by immune stimulation is not necessarily accompanied by selective impairment in learning or memory.