Effects of social isolation on LPS-induced hippocampal amyloid-beta expression and cognitive dysfunction in C57BL6/J mice

• Published in: Brain, behavior, and immunity Vol. 66; p. e13
• Main Authors: Peterman, J.L., Eimerbrink, M.J., White, J.D., Boehm, G.W., Chumley, M.J.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.11.2017
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2017.07.057

The connection between inflammation and various disease states is strongly affirmed in the existing literature, along with the connection between stress and immune function. Of particular interest is the connection between psychological stress and Alzheimer’s disease (AD), as clinical data have shown that stress is a risk factor for dementia-related dysfunction. Here we present data from a series of studies designed to examine the relationship between stress, inflammation, and amyloid-beta production. First we examined how two different durations of social isolation, acute (6days) or chronic (28days), influence the inflammatory response to lipopolysaccharide (LPS). Results from this study provide evidence that both manipulations are capable of exaggerating the inflammatory response to LPS. Following this, we studied the effect of stress on inflammation-induced amyloid-beta production in a non-transgenic model using C57BL6/J mice. After completion of both stress protocols, animals were treated with either LPS or saline once per day for seven consecutive days. Cognition was assessed using the contextual fear conditioning paradigm, and hippocampal tissue was extracted for amyloid-beta protein level quantification. LPS-induced elevations in hippocampal amyloid-beta are sufficient to induce cognitive deficits in a contextual fear conditioning paradigm. Furthermore, preliminary results suggest that stress and immune function may interact to increase amyloid-beta production, the protein responsible for plaque formation in AD.