Quick Project Snapshot
The role of peroxinitrite in depression
Nitric oxide (NO) is a gaseous messenger molecule involved in the regulation of signalling of a number of neurotransmitter systems, including serotonin and dopamine, which are systems underlying the neurochemical basis of mood and emotion. NO is also involved in cellular damage by forming the peroxynitrite (-ONOO) radical when combined with the superoxide anion, generating oxidative and nitrosative stress in the brain. A number of studies indicate that oxidative and nitrosative stress is implicated in neuropsychiatric disorders such as major depression. Our laboratory works with novel compounds that potently scavenge the –ONOO radical, which we have shown to be effective in animal models of Parkinson’s disease, a neurodegenerative disorder where oxidative and nitrosative stress are strongly implicated. This project will probe the involvement of the –ONOO radical in the neuropsychiatric disorder, depression, testing the hypothesis that –ONOO scavenging will positively influence depression-related behaviours in animal models of depression. The project will employ pharmacological tools to scavenge –ONOO and to probe the serotonergic neurotransmitter system. Skills learned will include an introduction to mouse behavioural analyses used in depression research, such as the forced swim test and measures of anhedonia, neuropharmacologial techniques to probe the serotonin system, and analyses of oxidative and nitrosative stress by Western blotting techniques.
This laboratory has expertise in Medicinal Chemistry (in association with Prana Biotechnology) and in biomarker discovery. More recently, it has focussed on the pathways leading to Parkinson’s disease, especially around the oxidative modifications of tau.
The Australian Imaging, Biomarker and Lifestyle (AIBL) Study, the Dementia Collaborative Research Centres (DCRC) and the Cooperative Research Centre for Mental Health (CRCMH). AIBL, DCRC and the CRCMH are intimately involved in our research programs, relying on patient cohorts for biomarker and imaging discovery in both neurodegenerative and psychotic illness.
Translation of our research findings into clinical practice will become more important over the next five years, as we move from a series of failed or equivocal phase 3 drug trials sponsored by the pharmaceutical industry. There is now general agreement that these drug trials need to be based at the earliest possible stage of Alzheimer’s disease, hence our participation in the Dominantly Inherited Alzheimer Network (DIAN) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (the A4 study). These two pre-clinical trials are designed to administer drugs in the preclinical phases of both familial and sporadic Alzheimer’s disease.
All Projects by this LabEffect of Abeta on excitotoxic signalling pathwaysEffect of tau phosphorylation on exosome release in cell culture systemsThe influence of alpha-synuclein on olfactionThe role of peroxinitrite in depressionThe role of tau protein in olfactory processesAre exosomes driving Alzheimer’s disease pathogenesis?Discovering how toxic proteins traffic from cell to cell in Alzheimer’s disease.Uncovering the role of exosome derived lipids in Alzheimer’s disease.
Dr Lachlan Thompson
Prof David Finkelstein
Scientists in the Neurodegeneration division interrogate how neurones live, die and can be rescued to improve brain function in degenerative conditions such as Parkinson’s and Motor Neuron Diseases. There is no effective treatment for Motor Neurone Disease and the incidence of Parkinson’s Disease is rising alarmingly in our aging community. Gene abnormalities, energy deprivation, toxic rubbish accumulation and inflammation all contribute to a toxic environment for brain cells. Our teams study these events in animal models and cultured cells, with a view to translating knowledge into new therapies for human patients.