Differential effects of duration and age upon the consequences of neuroinflammation in the hippocampus

• Published in: Neurobiology of aging 2013-04, Vol.34 (10), p.2293-2301
• Main Authors: Bardou, Isabelle, Brothers, Holly M., Kaercher, Roxanne M., Hopp, Sarah C., Wenk, Gary L.
• Format: Article
• Language: English
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2013.03.034

The current study investigated the hypothesis that the duration of the pro-inflammatory environment plays a critical role in the brain’s response that result in negative consequences upon cognition, biochemistry and pathology. Lipopolysaccharide (LPS) or aCSF was slowly (250 ηg/hr) infused into the IV th ventricle of young (3 mo), adult (9 mo) or aged (23 mo) male F-344 rats for 21 or 56 days. The rats were then tested in the water pool task and endogenous hippocampal levels of pro- and anti-inflammatory proteins and genes as well as indicators of glutamatergic function were determined. The duration of the LPS infusion, as compared to the age of the rat, had the greatest impact upon 1) spatial working memory, 2) the density and distribution of activated microglia within the hippocampus, and 3) the cytokine protein and gene expression profiles within the hippocampus. The duration- and age-dependent consequences of neuroinflammation may explain why adult humans respond positively to anti-inflammatory therapies while aged humans do not.