Behavioural fever and its underlying molecular mechanisms

Fever implies a significant increase in corporal temperature that aids toward the resolution of infective processes such as viral disease. The majority of vertebrate species are not homeothermic therefore must rely upon the environment for temperature regulation. Here we show that in the zebrafish an artificial viral infection, induced by poly (I:C), induces a fever response regulated by the behavioral choice of temperature. We recorded 12 h of the diurnal cycle in zebrafish previously treated (first 12 hours dark cycle) with the pyrogen, poly (I:C) [10 μg⋅kg-1]. Fish, n=10, were held in a thermal gradient (36-180C) separated into 7 interconnected chambers. Presence or absence of individuals in each chamber was recorded each 15 minutes throughout the 12 hour period. After the experimental period we dissected whole brains for microarray analysis. In monitored zebrafish intraperitoneal treatment with poly (I:C) induced a febrile behaviour with significantly elevated temperature preference (T of about 32ºC) in stark contrast with the observed frequency for saline-injected fish (28ºC). Microarray analyses uncovered significant shifts in transcriptional activity that were highly directed in the poly (I:C)-treated fish housed in the thermal gradient. When compared to gene expression profiles from poly (I:C)-treated fish deprived of a thermal gradient we observed a less intense specific to the poly (I:C) challenge and interestingly observed a scattered generalised stress response. Our results highlight the influence of temperature preference in the development of the immune response in zebrafish. Fever induced gene expression in zebrafish brain was measured at 24 after intra peritoneal injection with 1mg*Kg-1 of Poly (I:C) in zebrafish. Four independent experiments were performed to explore the transcriptomic profile induced by animals injected by Poly (I:C) with/whithout thermal gradient, saline solution (PBS), or control using different animals for each experiment.