Meeting Abstract

S7.1-2  Monday, Jan. 6 08:30  The impact of Toxoplasma gondii on host behaviour: can this parasite play a role in some cases of human schizophrenia? WEBSTER, J.P.*; KAUSHIK, M; Imperial College London Faculty of Medicine; Imperial College London Faculty of Medicine joanne.webster@imperial.ac.uk

Recognition of the role of infectious agents in a range of both acute and chronic diseases is increasing. One key example is the potential epidemiological and neuropathological association between some cases of schizophrenia with exposure to the protozoan Toxoplasma gondii. T. gondii establishes persistent infection within the CNS and can alter host behaviour. Altered dopamine levels have been reported for both T. gondii infection and schizophrenia. Moreover, several of the medications used to treat schizophrenia and other psychiatric disease demonstrate anti-parasitic, and in particular anti-T. gondii, properties in vitro. Furthermore, it appears that the parasite itself may actually be a source of this neurotransmitter. T. gondii was found to encode a copy of the mammalian enzyme tyrosine hydroxylase (TgTH), which represents the rate-limiting step in dopamine synthesis, through synthesis of L-DOPA, the precursor to dopamine. Using the epidemiologically and clinically applicable rat-T. gondii model system, we demonstrated that, whilst T. gondii appears to alter the rats' perception of predation risk, turning their innate aversion into a ‘suicidal’ feline attraction, anti-psychotic drugs proved as efficient as anti-T. gondii drugs in preventing such behavioural alterations and parasite establishment in the CNS in vivo. Furthermore we have identified a role of the T. gondii-produced TgTH in increasing activity levels, which in turn is correlated with reducing generalised anxiety. We have also established that T. gondii differentially alters activity levels depending on proximity to feline odour, causing more active rats to decrease activity when near a feline thereby providing further evidence for sophisticated selective manipulation to increase risk of predation by the definitive host.