Identifying Genetic Pathways Underlying The Development Of Distinct Neuronal Subtypes Among Midbrain Dopamine Neurons.
Funder
National Health and Medical Research Council
Funding Amount
$462,709.00
Summary
There is an urgent need in the field of Parkinson's disease (PD) research to develop new strategies aimed at halting progression of the disease (neuroprotection) and alleviaing the symptoms (restorative therapy). This project employs a novel and innovative design to identify genes expressed specifically by the cell type most effected in PD and therefore provide new genetic targets for neuroprotective and resorative therapy.
Changes In Motoneurone And Motor Axon Properties Distal To The Lesion In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$367,530.00
Summary
Following a stroke, adaptive changes occur in spinal cord motoneurones below the level of the stroke, but these are poorly understood. Apart from the exaggeration of spinal reflexes, distal changes have largely been neglected by clinicians. Even the mechanisms responsible for the exaggeration of spinal reflexes are still debated, in part because no single process can account for it. Using novel experimental techniques originally developed to study biophysical properties of human peripheral nerve ....Following a stroke, adaptive changes occur in spinal cord motoneurones below the level of the stroke, but these are poorly understood. Apart from the exaggeration of spinal reflexes, distal changes have largely been neglected by clinicians. Even the mechanisms responsible for the exaggeration of spinal reflexes are still debated, in part because no single process can account for it. Using novel experimental techniques originally developed to study biophysical properties of human peripheral nerves, this project will quantify the changes in excitability that occur in motoneurones and their peripheral extension, the motor axon, and compare these with the findings on the non-paralysed side of the same patients and with healthy matched control subjects. The changes that occur over time will be documented in longitudinal studies. The findings will be correlated with the patient's clinical status, providing insight into the extent to which changes in motoneurone properties drive clinical manifestations such as spasticity. In addition, control studies will provide further insight into whether disturbed transmission in some specific spinal reflex pathways contributes significantly to spasticity. The project is important for understanding the nature of adaptive changes (plasticity) in neural structures following lesions in the central nervous system and will shed light on the remote changes that occur in stroke. The studies are relevant not only for understanding current deficits but also for understanding and perhaps altering outcomes using rehabilitation procedures.Read moreRead less
To Understand The Role Of The Plasminogen Activating And Matrix Metalloproteinase Systems In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$499,321.00
Summary
Tissue-type plasminogen activator (t-PA) is known for its role as a clot dissolving protein. It is present in the brain and following traumatic brain injury (TBI), it can worse brain cell damage. We have established a mouse model of TBI . We will compare brain damage in mice that are deficient in or have high amounts of t-PA. We will also determine whether the recovery rate post-TBI can be improved using specific t-PA blockers. This project may provide new therapies for TBI.
Effects Of Muscle Inflammation On Sensory Neuron Excitability
Funder
National Health and Medical Research Council
Funding Amount
$397,398.00
Summary
Muscle pain is a common and poorly treated health problem for many Australians. This project examines the properties of nerves that sense muscle pain and looks at how these change during inflammation, a common cause of muscle pain. We are looking specifically at jaw muscles, which are one of the most common sites of chronic muscle pain. By understanding how muscle nerves are changed by injury, we hope to be able to develop treatments to prevent or reverse these changes.
Cellular Mechanisms Underlying Neurodegenerative Disease And The Neuronal Response To Trauma
Funder
National Health and Medical Research Council
Funding Amount
$406,264.00
Summary
Brain and spinal cord injury are major causes of death and disability, with degenerative diseases similarly affecting large proportions of the population. The singular objective of my research proposal is to increase our understanding of the molecular and cellular processes by which nerve cells respond to trauma and diseases such as Alzheimer’s and Parkinson’s, and to identify new therapeutic approaches aimed at encouraging the repair of damaged cells.
Neuroprotection By Ndfip1 In Brain Injury - Identifying Targets And Understanding Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$836,225.00
Summary
Brain injury from trauma and motor vehicle accidents is a serious health issue, affecting approximately 30,000 Australians per year. About 10% of the victims suffer serious long term consequences, including mental, physical and behavioural impairment. We have discovered a new brain protein capable of preventing neurons from dying following injury. This grant will improve our understanding of how this protein works, and provide a scientific foundation for devising therapies.
The Neural Reaction To Injury: Clues To The Cause And Prevention Of Acquired Brain Damage And Alzheimer's Disease.
Funder
National Health and Medical Research Council
Funding Amount
$390,326.00
Summary
The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the compl ....The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the complex cellular and gene expression changes that determine the ultimate fate of the cell. Both acquired brain injury and degenerative conditions such as Alzheimer?s disease represent an enormous health, social and economic burden. Furthermore, with predictions that Alzheimer?s disease will increase by 3-4 times by the middle of the next century due to the Oaging? of the population, it is becoming even more crucial to establish effective therapeutic interventions. The animal models investigated in this project can be used to unravel the crucial neuronal alterations associated with head trauma and the early stages of Alzheimer?s disease and, more importantly, may be the key to discovering novel strategies to prevent neuronal degeneration in these conditions.Read moreRead less
Therapeutic Development Of A Novel EphA4 Antagonist For Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$687,105.00
Summary
Spinal cord injuries impose a significant burden on patients and their carers. At present, there are no treatments for spinal cord injury that provide functional improvement. This research program will develop a novel therapeutic molecule, EphA4-Fc, which promotes axonal regeneration and delivers significant functional improvement. We will determine the most effective protocol for EphA4-Fc administration and the physiological and functional outcomes of these treatment regimes.
Cellular And Molecular Mechanisms Of Development And Regeneration In The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$345,773.00
Summary
During development of the fetal brain, cells are wired together. The correct wiring patterns are essential for normal function of the brain. Growth and formation of new connections decreases after birth. For this reason, the repair of the damaged adult nervous system is limited. However, there is one region in the nervous system that exhibits continual growth and repair throughout life. This is the nerve that is responsible for smell and connects the nose to the brain. The aim of this study is t ....During development of the fetal brain, cells are wired together. The correct wiring patterns are essential for normal function of the brain. Growth and formation of new connections decreases after birth. For this reason, the repair of the damaged adult nervous system is limited. However, there is one region in the nervous system that exhibits continual growth and repair throughout life. This is the nerve that is responsible for smell and connects the nose to the brain. The aim of this study is to identify the processes that permit continual growth within this region of the nervous system.Read moreRead less