To Determine The Role And Mechanism Of Action Of Tissue-type Plasminogen Activator In The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Tissue-type plasminogen activator (t-PA) is used clinically to remove blood clots. Recently, a role for t-PA in the brain was discovered where under pathological conditions it can promote ischaemic and excitotoxic brain injury. This project will examine the mechanisms by which t-PA promotes injury to brain cells. It is anticipated that results obtained could be used to devise a means to reduce t-PA toxicity in the brain that would be of therapeutic benefit for patients with ischaemic stroke.
The Effects Of Phencyclidine On The NMDA Receptor-neuregulin1 Signalling Complex: Implications For Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$433,872.00
Summary
Phencyclidine is the best known pharmacological agent that can induce schizophrenia-like symptoms in humans and animals. Recent research has strongly suggested that neuregulin1 and ErbB4 signalling are involved in schizophrenia pathology. This study will be the first to determine whether neuregulin1 is altered by phencyclidine, which will further our knowledge by re-evaluating the causal role of neuregulin1 in schizophrenia.
A Novel Marker Of Distressed Neurons In The Hypoxic Brain: Regulation, Function And Potential Clinical Utility.
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
The brain is easily damaged by lack of oxygen (hypoxia). We have recently identified a novel protein called GLAST1b which is expressed in distressed neurons. This protein is a glutamate transporter. Glutamate is implicated as a toxic agent hypoxia. This study will investigate what regulates the expression of GLAST1b, what the consequences of expression are, and whether this marker can be developed as a diagnostic tool for identifying the presence of, and distribution of brain damage.
It is now well established that there are genetic factors contributing to risk of depression but it is far from clear what these are and how they interact with environmental risk factors such as stressful life events (SLE) and poor social support (SS). A recent, highly cited paper has claimed that those carrying a particular genotype at the sertonin transporter gene are much more badly affected by stressful life events than other genotypes, and that this puts these people at much higher risk of ....It is now well established that there are genetic factors contributing to risk of depression but it is far from clear what these are and how they interact with environmental risk factors such as stressful life events (SLE) and poor social support (SS). A recent, highly cited paper has claimed that those carrying a particular genotype at the sertonin transporter gene are much more badly affected by stressful life events than other genotypes, and that this puts these people at much higher risk of depression. If true, this could have important practical implications for preventative mental health, in identifying those at greatest risk if depression and counselling them to avoid stressful situations. However, success in replicating this finding has been mixed, and this is possibly because another important risk factor, social support, has not been taken into account. We have DNA samples from over 5000 twins who have been assessed for depression and risk factors including SLE and SS. This will give us unprecedented power to estimate the importance of the genotype x environment interaction. We shall also type other genes that have been implicated in depression and check for interactions with life events and social support. Our results will inform preventative strategies in mental health practice.Read moreRead less