The Role Of Gliosis In Advanced Retinal Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$457,785.00
Summary
The development of treatments that restore vision assumes that the output neurons of the retina remain intact. Yet, there is now considerable evidence that the neurons that signal from the retina to the brain are altered in those that have degenerative diseases of the retina. Here, we will examine the cause of these cellular changes in an animal model and seek to prevent the loss of output neurons. This information is crucial for the development of treatments that seeks to restore vision.
The Cystine Glutamate Antiporter And Classical Glutamate Transporters In Normal And Pathological Brains And Retinae
Funder
National Health and Medical Research Council
Funding Amount
$416,000.00
Summary
This project will examine the role of a system that transports a toxic neurotransmitter, glutamate out of cells where it is relatively harmless, into the space surrounding nerve cells where it can be highly toxic. Previous models for the aberrant release of glutamate under pathological conditions such as strokes, have relied on the notion that other specialised glutamate transporters which normally work to remove glutamate from the space surrounding nerve cells, actually reverse their direction ....This project will examine the role of a system that transports a toxic neurotransmitter, glutamate out of cells where it is relatively harmless, into the space surrounding nerve cells where it can be highly toxic. Previous models for the aberrant release of glutamate under pathological conditions such as strokes, have relied on the notion that other specialised glutamate transporters which normally work to remove glutamate from the space surrounding nerve cells, actually reverse their direction of action and release glutamate. The current study investigates a transport system (called the cystine-glutamate antiporter) where the normal direction of action is to release glutamate. This system has been overlooked despite evidence that it could be involved in releasing glutamate and thus contribute to the death of nerve cells in a variety of human pathologies including glaucoma of the eye, epilepsy, and brain damage that occurs when the blood supply to the brain is interrupted, such as after a heart attack. This study examines both human tissues and animal models of disease states to determine if similar transport systems are present and if the cystine-glutamate antiporter might contribute to human nervous diseases. The function and distribution of the cystine-glutamate antiporter will be compared with classical transporters, under normal and pathological conditions, including situations where we have shown that it is possible to experimentally perturb normal glutamate transporter expression.Read moreRead less
Properties And Functions Of Reactive Astrocytes And Their Role In Neurological Disease
Funder
National Health and Medical Research Council
Funding Amount
$344,652.00
Summary
I am a developmental neuroscientist interested in the way alterations to normal brain development affect neuronal function later in life. I intend to investigate this by studying astrocytes – the cells that support and nourish brain nerve cells. In some diseases these astrocytes become stressed and instead of aiding the brain, set about destroying it. A better understanding of their action during development and disease may enable improved interventions for the treatment of many brain disorders.
Microglia As Primary Drivers Of Stress-induced Changes In Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$475,781.00
Summary
Persistent exposure to stressful events can produce serious and lasting disturbances in cognitive function. Our research group has recently identified that microglia may play a very significant role in these disturbances. The studies to be undertaken in this proposal will provide fundamental knowledge on how microglia contribute to neuronal plasticity, and how microglia via their effects on neurons regulate complex cognitive behaviour.
Using Astrocytes To Protect The Brain From Injury: Investigating Mechanisms And Therapeutic Strategies.
Funder
National Health and Medical Research Council
Funding Amount
$374,310.00
Summary
Brain damage caused by hypoxia (lack of oxygen) is a common problem in babies and can lead to outcomes ranging from cerebral palsy to death. We have a limited understanding of the mechanisms that cause damage, and thus very limited treatments. This project will investigate the role of cells called astrocytes in brain injury and identify novel therapeutic strategies to prevent or reverse brain damage. The outcomes of this research will ultimately lead to new treatments for hypoxic brain injury.
Microglial Paralysis In Post-stroke Neurodegeneration: Help Or Hindrance?
Funder
National Health and Medical Research Council
Funding Amount
$512,351.00
Summary
Dementia and cognitive decline may occur months or years after a stroke, associated with delayed loss of brain cells in different brain regions. We recently discovered that the cells responsible for protection and repair of brain, called microglia, become paralysed in these regions. We will use a live-imaging microscope to determine whether the microglial paralysis causes brain cell death. We will also determine if a commonly used stroke prevention drug can worsen the microglial paralysis.
Abnormalities in cells at the back of the eye called photoreceptors are associated with at least 50% of all cases of blindness in this country.This project will examine a novel mechanism of photoreceptor death. In particular, whether abnormalties in support cells at the back of the eye cause photoreceptors to lose contact with their nutrient source and die.
Metabotropic Glutamate Receptors: Pharmacological Studies Of Receptor Subtypes In Neuronal Injury.
Funder
National Health and Medical Research Council
Funding Amount
$145,770.00
Summary
Glutamate is the major transmitter of excitatory information in the mammalian brain. Disruption of glutamate-mediated signaling between brain cells results in high extracellular levels of glutamate which is toxic to neurones. A recently discovered family of signal transducers, the metabotropic glutamate receptors, has been found to be localized on neurones and is switched on by these toxic glutamate levels. The roles of these metabotropic glutamate receptors in neurotoxicity is essentially unexp ....Glutamate is the major transmitter of excitatory information in the mammalian brain. Disruption of glutamate-mediated signaling between brain cells results in high extracellular levels of glutamate which is toxic to neurones. A recently discovered family of signal transducers, the metabotropic glutamate receptors, has been found to be localized on neurones and is switched on by these toxic glutamate levels. The roles of these metabotropic glutamate receptors in neurotoxicity is essentially unexplored and is the topic under investigation in this project. How their activation affects cellular signaling switch on will be investigated to gain an understanding of the roles metabotropic glutamate receptors play in acute brain injury (eg stroke) and chronic neurodegenerative conditions (eg Huntington's chorea and Alzheimer's disease).Read moreRead less
Neuron To Glia Signalling: Learning How Synaptic Signalling Can Promote CNS Remyelination
Funder
National Health and Medical Research Council
Funding Amount
$609,650.00
Summary
An immature cell type in the brain, known as the oligodendrocytes progenitor cell (OPC), receives direct electrical communication from neurons. This communication regulates the behavior of the OPC, affecting its ability to divide and generate new brain cells. This project will identify the signaling molecules that guide the OPC to for this specialized contact with the nerve cell. Understanding this communication has important implications for the treatment of Multiple Sclerosis.