Neuroimmune Interactions Mediating Sickness Behaviour During Trypanosoma brucei brucei Infection in Experimentally Infected Wistar Rats

Trypanosoma brucei brucei causes sickness behaviour in experimentally infected animals characterised by reduced locomotion, hypophagia, hypersomnia, and anhedonia, which impair productive performance and welfare in affected livestock. The neurobiological mechanisms underlying these behavioural manifestations involve complex neuroimmune signalling pathways through which peripheral inflammatory cytokines communicate with the central nervous system to modulate behaviour. This study delineated the neuroimmune mechanisms mediating sickness behaviour in Wistar rats experimentally infected with T. brucei brucei, with translational relevance to livestock trypanosome infection in endemic zones of Nigeria including Kwara, Benue, and Nasarawa states. Forty rats were infected intraperitoneally with 10 to the fourth power trypanosomes per animal and monitored alongside 20 sham-infected controls for 28 days. Sickness behaviour was quantified by open field activity, sucrose preference, and forced swim tests at weekly intervals. Parasitaemia, serum and cerebrospinal fluid cytokine profiles, hypothalamic prostaglandin E2, and blood-brain barrier integrity by IgG immunohistochemistry were assessed at days 7, 14, and 21 post-infection. Cyclooxygenase-2 and indoleamine 2,3-dioxygenase expression in hypothalamic and hippocampal tissues were characterised by western blot. Infected rats showed progressive reduction in locomotion, sucrose preference, and food intake correlating with parasitaemia. Cerebrospinal fluid IL-1 beta and TNF-alpha were significantly elevated from day 7, preceding blood-brain barrier disruption detected at day 14. Hypothalamic COX-2 and IDO-1 were significantly upregulated. Selective COX-2 inhibition with celecoxib partially reversed sickness behaviour. These findings elucidate the prostaglandin-mediated neuroimmune pathway as a primary driver of trypanosomosis-associated sickness behaviour with therapeutic implications. Keywords: trypanosomosis, sickness behaviour, neuroimmune, cyclooxygenase-2, prostaglandin.