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A Breakdown Of Cortical Homeostasis In Depression: A Focus On The Anterior Cingulate
Funder
National Health and Medical Research Council
Funding Amount
$625,629.00
Summary
Major depressive disorders affect 20% of the Australian population. Some symptoms of major depressive disorders arise because of a dysfunction of the human brain, particularly the cortex. Our studies show there are biochemical changes in the anterior cingulate cortex in people with mood disorders. We will now extend our studies to show there is a breakdown in the balance between neurotransmitter and neuroinflammation pathways in the anterior cingulate cortex in major depressive disorders.
A Novel Mechanism For Therapeutically Modulating Neurotransmitter-activated Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$667,529.00
Summary
This project aims to elucidate the mechanisms by which macrocyclic lactones bind to brain ion channel receptors. This will reveal fundamental new insights into the operation of these receptors and will have important implications for the design of novel treatments for a variety of central nervous system disorders.
Investigation Of Novel Therapeutic Targets For The Treatment Of Drug Addiction
Funder
National Health and Medical Research Council
Funding Amount
$294,892.00
Summary
Drug abuse remains one of the world’s leading health care problems and the current drugs available to treat drug addiction are largely ineffective. This project aims to investigate the potential of a novel therapeutic target for the treatment of drug addiction with has the capacity for substantially reduced off-target effects.
Inhibitory Neurotransmitter Receptors As Therapeutic Targets For Chronic Pain And Anxiety Disorders
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
There are currently few effective long-term treatments for chronic pain and anxiety disorders. Here we propose to develop innovative therapies for both of these debilitating neurological disorders. In addition, we plan to improve our current understanding of how these disorders occur in the first place. This may identify novel potential therapeutic strategies for treating pain, anxiety and a host of other neurological disorders.
Anxiety and addiction are disorders with high co-morbidity that present a major worldwide public health concern. Treatment in both cases often involves an approach called extinction which helps to reduce the relapsing nature of these disorders. This grant is designed to examine the role of a specific protein in addiction and anxiety, by virtue of its involvement in the process of extinction.
Understanding The Pathophysiology Of Schizophrenia, Major Depressive Disorder And Bipolar Disorder As A Basis For Improving Treatments
Funder
National Health and Medical Research Council
Funding Amount
$804,106.00
Summary
The Applicant seeks to understand the causes of the schizophrenia, bipolar disorder and major depressive disorder, which affect over 20% of the Australian population. This research is important as drug design, based on chemical remodelling, has not significantly advanced initial breakthroughs in treating psychiatric disorders and there is now a widespread belief that new drugs will only come from understand their causes.
Novel Radiolabelled Peripheral Benzodiazepine Receptor (PBR) Ligands For Imaging And Treating Neuroinflammation
Funder
National Health and Medical Research Council
Funding Amount
$425,460.00
Summary
Neuroinflammation is involved in chronic, slowly progressive neurodegenerative diseases such as Multiple Sclerosis, and Alzheimer's, Parkinson's and Huntington's Diseases. A signifiacnt and early charactersitic in the development of neuroinflammation and the progression of these diseases is the damaging changes that occur to specific cells called glial cells in the brain. Termed microglial activation these changes cause regions of the brain to succumb to progressive disease and tissue destructio ....Neuroinflammation is involved in chronic, slowly progressive neurodegenerative diseases such as Multiple Sclerosis, and Alzheimer's, Parkinson's and Huntington's Diseases. A signifiacnt and early charactersitic in the development of neuroinflammation and the progression of these diseases is the damaging changes that occur to specific cells called glial cells in the brain. Termed microglial activation these changes cause regions of the brain to succumb to progressive disease and tissue destruction. The ability to pickup early signs of injury or to measure destructive changes to glial cells in the brain using noninvasive imaging techniques would be of great value in the clinical diagnosis and management of neurodegenerative disease. The ubiquitous nature of these activated microglia also makes the microglia a target for the development of pharmacological approaches to the treatment or prevention of many central nervous system diseases. Researchers at ANSTO and the ANU have developed a novel class of molecules, which target a specific protein called the peripheral benzodiazepine receptor or PBR which is enhanced in damaged glia. Radiolabelled analogues of these molecules have demonstrated a strong correlation between inflammation and the expression of this receptor in various animal models of inflammation and neurodegeneration. Furthermore, these molecules have the potential to inhibit further damage to these glial cells and could potentially slow down the progression of the disease. Therefore, further development of these molecules both as radiopharmaceuticals for noninvasive medical imaging and-or as inhibitors of microglial activation could have a significant impact on the understanding, management and treatment of neurodegenerative disease.Read moreRead less
Debilitating anxiety disorders, such as post-traumatic stress disorder or panic disorder, affect 14% of adult Australians and current therapy is often ineffective. The amygdala is a brain region that is key to learning fear responses but also in reducing our fear responses. This project will determine whether the brain’s own endogenous opioids can modify the activity of the amygdala in order to provide new leads for novel pharmacotherapies with enhanced efficacy.
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.
Muscarinic Receptors In The Human Brain: In Health And In Sickness
Funder
National Health and Medical Research Council
Funding Amount
$394,408.00
Summary
Schizophrenia is a severe mental illness, with sub-optimal treatment outcomes. New drugs are being designed to provide more effective treatment. To understand the effects of these drugs, we need to know which brain cells have the protein these new drugs target and which cells are affected in schizophrenia. Our project will determine the localisation of this drug target; this knowledge will help the development of better treatments for schizophrenia.