The effect of Toxoplasma gondii on host behaviour: Studies on evolution and mechanisms of action

Toxoplasma gondii affects a range of intermediate and secondary host species, including humans, with cats (Felidae) being the definitive host. The mechanism of action of T. gondii in its natural rat host can provide profound insights as to evolutionary trajectory of parasite manipulation. I used a range of non-invasive behavioural and physiological assays to assess the impact of infection on different aspects of innate rat behaviour. One key unique focus was an examination of the potential effect(s) of novel genetically modified parasite lines that overexpress tyrosine hydroxylase (TgTH) in comparison to wildtype T. gondii. The aim here was to test the hypothesis that TgTH, through its subsequent impact on neuromodulator levels, plays a significant mechanistic role in host behaviour modification. Consistent with previous studies, there was a clear effect of T. gondii on host behaviour, with effects seen in generalised anxiety and feline response tests. However contrary to predictions, there was little or no significant differences between wildtype and TgTH overexpressor infected rats in feline response tests, implying that TgTH does not play a major role in feline or olfactory related predation response. The implications of the role of TgTH in generalised anxiety and activity levels were more mixed. This suggests that other mechanisms of action, probably multiple, are involved. This work increases our understanding of the potential mechanisms this parasite has evolved to attain specific manipulation of the rodent intermediate host to increase transmission success to the feline definitive host. The results thus have both evolutionary implications for parasite-altered behaviour in intermediate host species, and applied implications in terms of the potential impact on health and behaviour of all infected hosts, including humans. Open Access