Ferroptosis in Schizophrenia

Research Opportunity
PhD students, Masters by Research, Honours students, Master of Biomedical Science
Number of Honour Places Available
2
Number of Master Places Available
1
Department / Centre
Psychiatry
Location
Florey Institute of Neuroscience & Mental Health
Primary Supervisor Email Number Webpage
Professor Christos Pantelis cpant@unimelb.edu.au 8344 1870 Personal web page
Co-supervisor Email Number Webpage
Professor Ashley Bush ashley.bush@florey.edu.au 9389 2914 Personal web page
Dr Carlos Opazo carlos.opazo@florey.edu.au 83444125

Summary Schizophrenia is a debilitating mental illness that disrupts the functioning of the mind, with onset typically occurring in young adulthood. Impairments in certain cognitive functions, such as working memory, are core features of Sz, which are not addressed for existing drug targets. Our general hypothesis is that schizophrenia is a complex disease resulting from a loss-of-function of key pathways that govern neurodevelopment, neurotransmission, intracellular redox state and synaptic connectivity. Our data indicate that iron is elevated in the orbitofrontal cortex in post mortem brain samples from individuals with schizophrenia relative to age- and sex-matched controls. We propose that a rise of cytosolic iron is upstream of key lesions associated with negative and cognitive symptoms of schizophrenia, including neuronal development (e.g., parvalbumin-interneurons and synaptic pruning), neurotransmission (e.g., GABAergic and glutamatergic pathways), as well as iron homeostasis, antioxidant defence (e.g., haem oxygenases), and ferroptosis (e.g., an iron-dependent pathway for lipid peroxidation recently associated with loss of parvalbumin-interneurons). The project aims to investigate the status of proteins involved in iron metabolim as well as levels of markers of oxidative stress.

Project Details

Our working hypothesis is that an elevation of iron in the brain of individuals with schizophrenia drives key neurochemical aspects of lipid peroxidative stress and hyperdopaminergia in the orbital frontal cortex that are known to be relevant to schizophrenia pathophysiology. Post mortem brain samples will be homogenized and centrifuged to collect protein supernantants. Oxidative stress induced cellular toxicity caused by unregulated lipid or iron metabolism will be biochemically measured DNA/RNA damage (8-hydroxydeoxyguanosine; 8-OHdG assay), lipid peroxidation (thiobarbituric acid reactive substances; TBARS assay) and protein carbonylation (Oxyblot assay). Proteins related to iron metabolims will be detected by Western blot.



Faculty Research Themes

School Research Themes

Neuroscience & Psychiatry



Research Opportunities

PhD students, Masters by Research, Honours students, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department / Centre

Psychiatry

Research Node

Florey Institute of Neuroscience & Mental Health

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