Peripheral inflammation affects the central nervous system and biology of the brain

Abstract

There is a growing pool of evidence to support the hypothesis that events in the periphery, particularly of an inflammatory nature, can have a profound effect on the central nervous system (CNS). Specifically, inflammatory cytokines have been shown to be important mediators of neuropsychiatric disorders and variations in their expression can affect the severity of both depression and disease score, if presenting with specific comorbidities. The mechanisms driving the relationship between the CNS and the periphery remain to be fully understood. To investigate this, we have used a well characterised model of psoriasis-like skin inflammation as a tool to examine the consequential effect of localised peripheral inflammation on the brain. Aldara cream, which contains 5% Imiquimod as the active component, has been shown to induce psoriasis-like skin inflammation when applied repeatedly to the dorsal skin of mice. We have already shown that this model leads to the transcriptional upregulation of a number of classic interferon-stimulated genes (ISGs) in the brain, a response that we do not see mimicked in the peripheral blood leukocytes (PBL) at the same time point. We have since identified the transcriptional upregulation of a number of chemokines in the CNS which may be important for instigating immune cell infiltration. Furthermore, we have found that Aldara treatment causes a reduction in the level of doublecortin staining in the dentate gyrus of the hippocampus, indicating a negative effect on neurogenesis. Finally, a basic behavioural model of anhedonia has allowed us to determine a phenotypic consequence of Aldaratreatment, whereby the burrowing activity of the treated group is significantly reduced compared with the control group.