Using Reward-based Biomarkers To Improve The Early Detection Of Bipolar Disorder In Individuals Seeking Treatment For Depression
Funder
National Health and Medical Research Council
Funding Amount
$366,252.00
Summary
Bipolar disorder is often misdiagnosed as unipolar major depression, which can have disastrous clinical consequences. Emerging evidence indicates that individuals with bipolar disorder show particular dysfunctions within brain regions involved in processing reward. This research will use cutting-edge neuroscience methodologies to investigate reward processing in these two disorders, with the objective of identifying biological markers that help distinguish bipolar from unipolar depression.
Dopamine Neuron Ontogeny: Convergent Neurobiological Pathway For Risk Factors Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$337,214.00
Summary
Schizophrenia is associated with changes in dopamine (a signalling molecule in the brain). These changes are present prior to psychosis, suggesting they begin early in development. Our aims are to manipulate key factors in the development of brain dopamine systems to clarify their role in psychosis and schizophrenia. This work has the potential to identify early brain changes that lead to schizophrenia, which in turn may generate better diagnoses and outcomes for people with this disorder.
The Role Of Meninges In Midbrain Dopamine Development
Funder
National Health and Medical Research Council
Funding Amount
$378,311.00
Summary
Dopamine neurons are important for the control of movement, emotion and cognitive function, and are affected in a number of disorders such as Parkinson’s disease. Instrumental in improving our knowledge of disease etiology and the development of new therapies will be a greater understanding of how these cells are initially born during development. This project examines the role of the brain’s meninges in dopamine development and repair and will identify proteins and signaling pathways involved.
Wnt Signaling In Dopaminergic Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
During development, the brain establishes intricate and precise connections. In several brain pathways, little is known about the processes regulating this connectivity. Furthermore, it is likely that the same processes will be required to repair the injured- diseased brain. This project builds on our preliminary data, that Wnt proteins are important regulators of developing dopamine pathways, and has implications for dopamine disorders including Parkinson’s disease and addiction.
Testing The Prion Hypothesis In Parkinson’s Disease Using A Novel In Vivo Model Of Α-synuclein Transmission
Funder
National Health and Medical Research Council
Funding Amount
$622,555.00
Summary
Parkinson’s Disease (PD) is a debilitating neurological disease with no cure. Recently it has been discovered that the disease can spread through the brain. We have developed the worlds first animal model to study exactly how the disease propagates inside of neurons during this spread. We will use the model to answer key questions about this critical stage of disease spread, knowledge that is essential for the development of successful therapies to prevent disease progression.
Standardising Protocols For The Differentiation And Integration Of Human Pluripotent Stem Cell-derived Neural Transplants In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$987,664.00
Summary
Clinical trials have shown that transplanting dopamine neurons (specific nerve cells) into the brain of Parkinson’s disease patients can improve symptoms. Trials use fetal tissue for implantation, which is unsustainable and highly variable. This proposal will examine stem cells as an alternative. We will establish a reliable protocol to instruct human stem cells to become dopamine neurons, develop methods to select these cells and, examine the integration of these transplanted cells in the brain
How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
The ability of humans to detect and be aware of errors in behaviour is a fundamental aspect of human cognition. As the saying goes: "To Err Is Human". This project seeks to understand how individual differences in our genetic makeup contribute to our ability to detect and be aware of errors in our behaviour. Understanding the biological systems underpinning error monitoring may assist in the treatment of many psychiatric disorders which are marked by poor awareness of behaviour.
Restoration Of The Nigrostriatal Pathway In The Parkinsonian Brain
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Many obstacles exist for cell transplantation in Parkinson's disease; namely poor restoration of the host brain circuitry due to incorrect graft placement. This results in incomplete motor function and unwanted side effects. Through iterative studies we endeavor to restore this circuitry by placing grafts in the appropriate location and promoting their survival and growth-integrations. This will require: optimizing the donor tissue and exposure of the graft to growth stimulating factors.
Wnt Signaling In Dopaminergic Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$564,721.00
Summary
A major obstacle in repairing the injured or diseased brain is inducing axons (nerve cell processes) to make the appropriate connections. This is especially true following cell replacement therapy (CRT) in Parkinson's disease (PD). We will examine the processes inducing axons in the dopamine pathways to grow. We hypothesize that Wnt signaling plays and important role and that therapeutic introduction of Wnt is required to repair the dopamine pathways following CRT in PD.