Molecular Control Of Interneuron Development And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$527,828.00
Summary
This project will study the changes that occur in neurons, during normal brain maturation and in pathology. We hypothesise that early signs of brain malfunction can be detected in neurons before symptoms appear. The role of a gene will be studied during development and disease in a mouse model of autism, in order to identify the molecular and electrical signs of abnormal activity. This research will ultimately enable us to propose new strategies to treat symptoms of brain disease.
Differential Regulation Of Human Tyrosine Hydroxylase Isoforms And The Development Of Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$325,591.00
Summary
Parkinson's disease is a common neurodegenerative disease whose major feature is loss of a dopamine containing nerves in a part of the brain called the substantia nigra. Loss of nerves within the substantia nigra is not uniform, but firstly and primarily affects the ventral cells, suggesting that particular dopaminergic neurons are more vulnerable to the disease process. A key to understanding Parkinson's disease would be to work out why these cells are more susceptible to degeneration than othe ....Parkinson's disease is a common neurodegenerative disease whose major feature is loss of a dopamine containing nerves in a part of the brain called the substantia nigra. Loss of nerves within the substantia nigra is not uniform, but firstly and primarily affects the ventral cells, suggesting that particular dopaminergic neurons are more vulnerable to the disease process. A key to understanding Parkinson's disease would be to work out why these cells are more susceptible to degeneration than other dopaminergic cells in the brain. Tyrosine hydroxylase controls the rate of dopamine synthesis. Humans are unique in that they contain four isoforms of tyrosine hydroxylase and therefore they have the potential to alter the regulation of dopamine synthesis in ways that other species do not. Recent developments in our laboratories have suggested that particular isoforms of tyrosine hydroxylase may have either a role in the susceptibility of dopaminergic neurons to degeneration in Parkinson's disease or a role in the timing of the symptoms of the disease. We have demonstrated differences in the distribution of the human TH isoforms within the substantia nigra, with certain isoforms being more prevalent in the susceptible ventral cells. We have also shown that there are major differences in the regulation of the four human tyrosine hydroxylase isoforms. Some isoforms will be more sensitive to conditions that occur with high frequency stimulation of neurons and some to low frequency sustained stimulation. This would provide a mechanism by which differential distribution of the human TH isoforms would result in altered dopamine synthesis in different parts of the human brain and this may in turn lead to either increased susceptibility to, or earlier appearance of symptoms of, Parkinson's disease.Read moreRead less
Development Of Pthaladyn-based Dynamin I-selective Inhibitors For Treatment Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$564,310.00
Summary
About 1% of the World�s population suffers from epilepsy; 30% fail to respond to anti-epileptic drugs (AED). Current AED development pathways have changed little in the past 20 years with the majority of current AEDs dampening the release of crucial chemical signals 24/7. Our new drugs, which inhibit a protein called dynamin, are only recruited at the onset of a seizure. Our approach will significantly enhance the day to day lives of those afflicted by epilepsy.
The Role Of Neuronal Hyperactivity And Neurotrophic Factor Signalling In Synaptogenesis, Dendrogenesis And Neuron Death In Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$700,331.00
Summary
Using mice with mutant genes causing amyotrophic lateral sclerosis, we will test whether motor neuron hyper-excitability during early development causes excessive synapse and dendrite formation, ultimately leading to neuronal death. We will also test whether activity-dependent secretion of neurotrophic factors and activation of their receptors plays a role in this disease. This will show whether neuronal hyper-activity and neurotrophic factor signaling plays a causal role in this disease.
The Role Of BDNF In Central Nervous System Myelination
Funder
National Health and Medical Research Council
Funding Amount
$478,235.00
Summary
Multiple Sclerosis (MS) is the most common neurological cause of disability in young adult Australians. The cause of MS is unknown and therapies are limited to reducing inflammation, which does not address the major problem of the disease: loss of myelin. This project directly investigates how myelin is formed and will identify key mechanisms in this process, which may eventually be developed into treatments for diseases such as MS.
Genetic Cues Responsible For Interneuron Migration And Layering In The Neocortex
Funder
National Health and Medical Research Council
Funding Amount
$650,250.00
Summary
Understanding how the brain is assembled, and the genes that drive this process, will provide insights into two exciting areas of current neuroscience. First, it will clarify how we differ from other species, and illuminate the evolutionary concepts underscoring functional specialization. Secondly, there are sound health-related reasons to study brain development. Proper brain function requires the proper assembly of neurons and the establishment of circuitry. Defective generation of neurons in ....Understanding how the brain is assembled, and the genes that drive this process, will provide insights into two exciting areas of current neuroscience. First, it will clarify how we differ from other species, and illuminate the evolutionary concepts underscoring functional specialization. Secondly, there are sound health-related reasons to study brain development. Proper brain function requires the proper assembly of neurons and the establishment of circuitry. Defective generation of neurons in sufficient numbers, or impediments to neuron migration to proper destinations are certain recipes for neurological disorders, including epilepsy and mental retardation. In this application, we will study how neurons are assembled in the cortex. We will focus on a subpopulation known as interneurons that are vital for toning down electrical discharges from excitatory neurons. We will investigate how these neurons are able to migrate long distances to settle into defined layers of the cortex. Mutant mice with deleted genes have a defect in this process and the aim of this project will be to study the precise mode of action for some of these genes.Read moreRead less