1. ¹Department of Molecular Virology, Immunology and Medical Genetics, Institute for Behavioral Medicine, The Ohio State University, Columbus, OH, USA
2. ²Integrative Neurobiology, INRA-CNRS-University of Bordeaux 2, Bordeaux cedex, France
3. ³Integrative Immunology and Behavior Program, University of Illinois, Urbana, IL, USA
4. ⁴Department of Animal Sciences, University of Illinois, Urbana, IL, USA
5. ⁵Department of Pathology, University of Illinois, Urbana, IL, USA

Correspondence: Dr RW Johnson, 4 Animal Sciences Laboratory, 1207 W Gregory Drive, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Tel: +1 217 333-2118; Fax: +1 217 333-8286; E-mail: rwjohn@uiuc.edu

Received 20 September 2007; Revised 30 October 2007; Accepted 6 November 2007; Published online 12 December 2007.

Abstract

Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted sickness response in aged mice with reductions in locomotor and feeding activities 24 and 48 h postinjection, when young adults had fully recovered. When submitted to the forced swim test 24 h post-LPS, both young adult and aged mice exhibited an increased duration of immobility. However, when submitted to either the forced swim test or the tail suspension test 72 h post-LPS, an increased duration of immobility was evident only in aged mice. This prolonged depressive-like behavior in aged LPS-treated mice was associated with a more pronounced induction of peripheral and brain indoleamine 2,3-dioxygenase and a markedly higher turnover rate of brain serotonin (as measured by the ratio of 5-hydroxy-indoleacetic acid over 5-hydroxyt-tryptamine) compared to young adult mice at 24 post-LPS injection. These results provide the first evidence that age-associated reactivity of the brain cytokine system could play a pathophysiological role in the increased prevalence of depression observed in the elderly.