Abstract
Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS) is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and depressive-like behavior in mice. We report that systemic administration of LPS induced astrocyte activation in transgenic GFAP-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice. Furthermore, LPS treatment caused a strong but transient increase in cytokine levels in the serum and brain. In addition to studying LPS-induced neuroinflammation, we tested whether sickness could be separated from depressive-like behavior by evaluating LPS-treated mice in a panel of behavioral paradigms. Our behavioral data indicate that systemic LPS administration caused sickness and mild depressive-like behavior. However, due to the overlapping time course and mild effects on depression-related behavior per se, it was not possible to separate sickness from depressive-like behavior in the present rodent model.
Highlights
Clinical depression is a devastating, recurrent psychiatric illness that has a lifetime prevalence of 16% [1]
We report that systemic administration of LPS induced astrocyte activation in transgenic glial fibrillary acidic protein (GFAP)-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice
Depression frequently occurs as a comorbidity of conditions that are characterized by a sustained, systemic inflammation such as rheumatoid arthritis [8, 9], coronary heart disease [10, 11], stroke [12], type 2 diabetes [13], and obesity [14]
Summary
Clinical depression is a devastating, recurrent psychiatric illness that has a lifetime prevalence of 16% [1]. Depression frequently occurs as a comorbidity of conditions that are characterized by a sustained, systemic inflammation such as rheumatoid arthritis [8, 9], coronary heart disease [10, 11], stroke [12], type 2 diabetes [13], and obesity [14] Another indication that inflammation and depression are linked comes from clinical observations in which therapeutic administration of the proinflammatory cytokines interleukin-2 and interferonα to cancer or hepatitis C patients resulted in depression in up to half of these patients [15,16,17]
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