Role of neuroinflammation and neurotransmitter systems in the improved cognition induced by estrogen receptor modulation

Cognitive deficits play a major role in the disability and poor quality of life of people with schizophrenia (e.g. inability to study or work, difficulty maintaining social relationships), and schizophrenia results in more than $3 billion in health-related costs in Australia annually. In clinical practice, there are no effective treatments for the cognitive deficits in schizophrenia. In a recent clinical trial the Schizophrenia Research Laboratory identified that a selective estrogen receptor modulator, raloxifene enhanced cognition in some people with schizophrenia. The precise mechanism whereby raloxifene enhances cognition is not clear.

This project aims to uncover the molecular and cellular mechanisms of action of raloxifene and the behavioural correlates that are improved by raloxifene in healthy rodents and in rodents with a schizophrenia-like phenotype. This will aid in prioritising downstream molecular targets to develop novel treatments aimed at reversing or preventing the MIA-induced cognitive deficits. The ultimate goal is to translate this information to develop treatments for the debilitating cognitive deficits of schizophrenia.