Invited Symposium: Cytokines, Monoamines and Behavior
To examine the relationship between chronic activation of the immune system and changes in brain function, we identified the autoimmune strain of MRL mice as a useful animal model. This strain of mice consists of the MRL-lpr substrain, which develops an accelerated form of lupus-like disease, and congenic MRL-+/+ substrain, which develops a late form of the disease. In parallel with the onset of autoimmune manifestations, MRL-lpr mice show a constelaltion of behavioral changes which we labelled 'autoimmunity-induced behavioral syndrome' (AABS). AABS is characterized by the appearance of an anxious/depressive-like behavioral state, and aberrant hippocampal/cortical morphology. As an initial step to identify which immune factor(s) induce these changes, we focussed on interleukin-6 (IL-6) because upregulation of this neuroactive cytokine coincides with the onset of AABS and brain neuropathology. Moreover, our recent studies showed that prolonged immunosuppressive treatment with cyclophosphamide abolished IL-6 production, normalized behavioral performance, and prevented cortical pathology. To test whether prolonged exposure to IL-6 produces behavioral effects, we infected healthy MRL +/+ and AKR/J strains of mice with an adenoviral vector carrying murine IL-6 cDNA. This treatment, shown to increase serum IL-6 over a 6-day period, reduced blood glucose levels, food, water, and sucrose intake, and lowered rectal temperature over 6 days in both strains. Although overall locomotor activity did not change, IL-6 infected AKR/J mice showed reduced exploration of a novel object. No other significant changes in behavior were noted. These results indicate that prolonged exposure to circulating IL-6 impairs consumatory behavior, possibly reflecting a lowered metabolic demand. It is hypothesized that sustained exposure to IL-6 induces a hypometabolic state that leads to lowered brain glucose supply and thus altered brain morphology and function.
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|Sakic, B; (1998). The Role of Interleukin-6 in Autoimmunity-induced Behavioral Dysfunction and Neurodegeneration. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/anisman/sakic0854/index.html|
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