Project Summary
This Project aims to find out if targeting the glutamate system can reverse dopamine dysregulation in the inflamed brain.
What is the issue for NSW?
Current treatments for schizophrenia are ineffective in ~30% of patients and can have severe side effects. There is an urgent need to understand the molecular changes that occur in the brains of people with schizophrenia so we can develop more effective treatments.
The research team has identified that schizophrenia can be categorised based on their state of midbrain inflammation. A better understanding of the effect of neuroinflammation on the neuropathological processes in the brains of people who have schizophrenia will help to identify and develop new ways to treat schizophrenia.
What does the research aim to do and how?
This research will create new knowledge about glutamate related changes in the brains of people with schizophrenia, with and without inflammation, and determine how these changes impact dopaminergic dysregulation.
The ability of potential new drugs to reduce inflammation in the brain and normalise dopamine neurotransmission, through modulation of glutamate receptors will be assessed. Post-mortem human brain studies and essential animal studies will be used to find the best candidates for testing in humans.
These studies will also increase our knowledge and understanding of drugs already being tested in humans. This research will:
- discover inflammatory cells and pathways contributing to the variability of the disease between patients, and in turn find useful biomarkers for the state of inflammation
- identify effective treatments that can reduce inflammation and restore dopamine neuron health
- generate knowledge about the state and cellular source of glutamate-related changes in the inflamed and non-inflamed human midbrain of people with schizophrenia.