Molecular Horizons Seminar - Dr Tertia Purves-Tyson (NeuRA)

Clinical and postmortem studies link neuroinflammation to the pathophysiology of schizophrenia. I will discuss our postmortem evidence for neuroinflammation contributing to dopamine dysregulation in schizophrenia, and our evidence for similar neuroinflammation in the midbrain in a maternal immune activation (MIA) rodent model of dopamine dysregulation. Schizophrenia is more prevalent in men than women, giving rise to the theory that estrogen is protective. The estrogen receptor modulator, raloxifene, can improve cognition and attenuate psychosis in schizophrenia. Like estrogen, raloxifene is proposed to have anti-inflammatory effects, however the precise cellular and molecular mechanisms underlying these effects are unclear. I will present data from adult offspring showing sex-specific dopamine-related behavioural changes following exposure to a prenatal immune insult, and the effect of raloxifene treatment on these behaviours. I will discuss immune-related molecular changes in the nigrostriatal pathway that may contribute to these sex-specific behavioural changes, and/or to raloxifene-induced changes in behaviour. Identifying the molecular mechanisms underlying MIA- and raloxifene-induced alterations in hyperdopaminergia and cognition in males and females is crucial for contributing knowledge to ultimately lead to improved treatment outcomes for schizophrenia.