Disruption of Circadian Rhythms in Synaptic Activity of the Suprachiasmatic Nuclei by African Trypanosomes and Cytokines

Abstract

Disturbances in biological rhythms pose a major disease problem, not the least in the aging population. Experimental sleeping sickness, caused by Trypanosoma brucei brucei, in rats constitutes a unique and robust chronic model for studying mechanisms of such disturbances. The spontaneous postsynaptic activity was recorded in slice preparations of the suprachiasmatic nuclei (SCN), which contain the master pacemaker for circadian rhythms in mammals, from trypanosome-infected rats. The excitatory synaptic events, which in normal rats show a daily variation, were reduced in frequency, while the inhibitory synaptic events did not significantly differ. This indicates selective disturbances in glutamate receptor-mediated neurotransmission in the SCN. Treatment with interferon-γ in combination with lipopolysaccharide, which has synergistic actions with cytokines, and tumor necrosis factor-α similarly caused a reduction in excitatory synaptic SCN activity. We suggest that changes in the synaptic machinery of SCN neurons play an important pathogenetic role in sleeping sickness, and that proinflammatory cytokines can mimic these changes.

Keywords

• circadian rhythms
• cytokines
• interferon-γ, sleeping sickness
• spontaneous synaptic activity
• suprachiasmatic nucleus
• trypanosomes