The Pharmacology And Physiology Of GABA-C Receptors
Funder
National Health and Medical Research Council
Funding Amount
$481,980.00
Summary
GABA is one of the most important chemicals in the brain. GABA and its associated receptors (GABA receptors) work together to keep the balance between neuronal excitation and inhibition which is required for normal brain function. There are three types of GABA receptors called GABA-A, GABA-B and GABA-C receptors. Chemicals acting at these receptors may be therapeutically useful in treating neurological probles such as epilepsy, anxiety, depression and memory-related disorders associated with Alz ....GABA is one of the most important chemicals in the brain. GABA and its associated receptors (GABA receptors) work together to keep the balance between neuronal excitation and inhibition which is required for normal brain function. There are three types of GABA receptors called GABA-A, GABA-B and GABA-C receptors. Chemicals acting at these receptors may be therapeutically useful in treating neurological probles such as epilepsy, anxiety, depression and memory-related disorders associated with Alzheimer's disease and schizophrenia. GABA-A and GABA-C receptors are members of the ligand-gated ion channel super family in which the ion channel forms an intergral and central part of the receptor. In response to GABA, the channel opens and chloride ions flow through the channel. This causes an inhibitory action i.e. the cell reduces its rate of firing. This project aims to study GABA-C receptors by investigating what proteins make up the ion channel, by studying the actions of a range of chemicals that have specific effects at these receptors and by identifying amino acids that are important for normal channel function. New chemicals identified in our studies will provide leads for the design and development of new therapeutic agents acting on the brain.Read moreRead less
Functional Integration Of Transplanted Neural Stem Cells In Huntingtons Disease
Funder
National Health and Medical Research Council
Funding Amount
$373,360.00
Summary
The proposed study investigates important questions related to restoration of brain functions in a neurodegenerative disease, Huntington's disease, using neural stem cells (precursors of nerve cells). It will expand our understanding of the mechanisms underlying the development of Huntington's disease, and provide insights into potential therapeutic use of neural stem cells for the currently incurable Huntington's disease.
Using Artificial Synapses To Investigate The Functional Pathology Underlying Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$515,256.00
Summary
Epilepsy is a common neurological disorder. Some forms arise from hereditary mutations to GABA-A receptors. To advance our understanding of epileptogenesis, it is necessary to understand how mutations affect GABA-AR function. We will use a novel ‘artificial synapse’ system to characterise these mutant receptors. This will define how epilepsy is caused and inform us how to best tailor drug treatments for different epilepsy conditions.
Oxytocin As A Novel Antagonist Of The Intoxicating And Addictive Effects Of Alcohol
Funder
National Health and Medical Research Council
Funding Amount
$739,106.00
Summary
Alcohol is Australia’s most harmful recreational drug and more effective treatments for alcohol abuse are desperately needed. The CIs have shown that administering oxytocin reduces alcohol intoxication and consumption, and prevents alcohol from acting at specific sites in the brain that are central to alcohol’s intoxicating and addictive effects. This project probes the effects of oxytocin at these sites and the potential utility of targeting this interaction to treat alcohol-use disorders.
Flavonoids are widely consumed in the diet in food, beverages and herbal preparations. They have diverse actions on the body. We wish to investigate how they might affect brain function. One of the most important transmitters in the brain is a chemical known as GABA. Many known CNS drugs, such as alcohol and the benzodiazepine Valium, influence the action of GABA as a transmitter. These drugs enhance the action of GABA in activating particular receptors in the brain. We have discovered that apig ....Flavonoids are widely consumed in the diet in food, beverages and herbal preparations. They have diverse actions on the body. We wish to investigate how they might affect brain function. One of the most important transmitters in the brain is a chemical known as GABA. Many known CNS drugs, such as alcohol and the benzodiazepine Valium, influence the action of GABA as a transmitter. These drugs enhance the action of GABA in activating particular receptors in the brain. We have discovered that apigenin, a flavonoid found in many herbal preparations and in beverages such as camomile tea, has a special action on GABA in that it enhances the enhancing action of benzodiazepines on GABA receptors. This is a novel mode of drug action that needs to be explored further. We will study the actions of a range of flavonoids known to occur in various popular products such as soy milk, red wine and green tea for their effects on GABA receptors. From the results we plan to design and synthesise new substances with a view to discovering new therapeutic agents to treat a range of CNS disorders, such as anxiety, epilepsy and memory deficits. This project will also yield information on the possible interactions between alcohol and prescription drugs like Valium with flavonoids consumed in the diet. Already it is known that a flavonoid in grape fruit juice may influence the metabolism of drugs like Valium. This project will be concerned with possible interactions within the brain. The novel mode of action that we have discovered is of significance in terms of our basic understanding of brain function. It could add another dimension to what we already know about the brain as our most complex organ.Read moreRead less
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.