Relationship Between Nigral Injury, Dopamine Handling And Dyskinesia In Parkinsonism
Funder
National Health and Medical Research Council
Funding Amount
$65,685.00
Summary
Parkinson's Disease is a disabling condition that results from loss of nerve cells (neurones) in the part of the brain known as the substantia nigra (SN). These neurones make dopamine. Symptoms become apparent when 80% of these neurones are gone, suggesting that compensation can occur in the brain. Dopamine can be replaced with the drug L-dopa. Unfortunately this benefit is not sustained and is frequently marred by the production of unpleasant writhing wriggling movements called dyskinesia. Thes ....Parkinson's Disease is a disabling condition that results from loss of nerve cells (neurones) in the part of the brain known as the substantia nigra (SN). These neurones make dopamine. Symptoms become apparent when 80% of these neurones are gone, suggesting that compensation can occur in the brain. Dopamine can be replaced with the drug L-dopa. Unfortunately this benefit is not sustained and is frequently marred by the production of unpleasant writhing wriggling movements called dyskinesia. These movements can also complicate the treatment for schizophrenia and other neurological conditions. The way the brain compensates for loss of SN neurones and why dyskinesia occur is unknown. However we present a hypothesis that the mechanisms for compensation also produce the dyskinesia. We have shown that an injury to the SN results in a compensatory response of vigorous sprouting of the surviving dopamine neurones. This sprouting may also explain why dyskinesias occur. The aim of this study is to establish whether the degree of compensatory response corresponds with the severity of dyskinesia and how this compensatory response can be modified or regulated.Read moreRead less
Glaucoma is a progressive, poorly understood blinding disease with limited treatment options. It is characterised by the death of the nerve cells in the eye whose fibres form the optic nerve. Results obtained in the current proposal will lead to a better understanding of key features of the early stages of the disease and, additionally, will explore the potential of a novel therapeutic approach based on regeneration of damaged nerve fibres within the optic nerve.
Axonal Regeneration And Degeneration: Cellular And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Understanding how to repair of nerve damage following a traumatic injury, a vascular accident, or a degenerative condition, is essential to develop novel effective treatments. We have identified, in a simple genetic model system, the molecular mechanisms that allow a transected nerve to be repaired by reattachment of its two separated fragments. This 'axonal fusion' process is a highly promising innovative approach that can be exploited to restore the original neuronal circuit.
Understanding Axonal Fusion: An Alternative Mechanism To Repair Injured Axons.
Funder
National Health and Medical Research Council
Funding Amount
$648,447.00
Summary
Being able to repair an injured nerve by stitching the two damages sections back together is an incredible challenge in neurosurgery, and a highly desired outcome for the surgeon as well as for the patient suffering a spinal cord or peripheral injury. We have discovered molecules that mediate nerve repair by favouring the reconnection of the two separated fragments. We will study how they function, and if they can be applied to repair injured mammalian neurons.
Nerve cells communicate with each other through nerve processes or neurites. The dysfunction of neurites results in the clinical symptoms of dementia such as cognitive decline. Currently we cannot directly monitor degeneration of neurites in the living brain and therefore it is difficult to determine whether therapeutic agents are protective. My goal is to develop a detection system in the blood that will allow us to monitor these changes during disease progression and therapeutic intervention.
Changes In Pelvic Autonomic Neurons After Spinal Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$176,734.00
Summary
This project is about the effects of spinal injury on autonomic neurons that control the bladder, lower bowel and reproductive organs. One of the consequences of some types of spinal injury is that there are no signals being sent from the spinal cord to the nerve cells outside the cord, and this leads to poor bladder control, impotence, etc. We are mimicking this problem experimentally by damaging the spinal nerves that carry these signals. We have found that after this type of damage the pelvic ....This project is about the effects of spinal injury on autonomic neurons that control the bladder, lower bowel and reproductive organs. One of the consequences of some types of spinal injury is that there are no signals being sent from the spinal cord to the nerve cells outside the cord, and this leads to poor bladder control, impotence, etc. We are mimicking this problem experimentally by damaging the spinal nerves that carry these signals. We have found that after this type of damage the pelvic autonomic neurons make many new connections between each other, and the types of new connections depend on which spinal nerves have been injured. This leads to the question: are these new connections good or bad? ie are they helpful in trying to get organ control back to normal or will they stop the correct connections from the spinal cord from being made in the future? This project addresses these questions by using sophisticated techniques for staining and visualising individual nerve fibres growing out from the spinal cord. We will track how well these fibres grow back and connect with the pelvic autonomic neurons. In particular, we will see whether they make correct connections, and if these connections are influenced by the new fibres that have grown between the autonomic neurons in the interim period. We will also do physiological tests to see if the new connections have the correct function. The ultimate aim of these studies is not only to understand more about regeneration, but to see what determines whether the correct connections have been made - and ideally, to give us insight into how we can make regeneration work more quickly and accurately. We believe that this work is an important adjunct to other studies on spinal injury, which mostly focuses on regaining voluntary motor control (e.g. walking); however loss of bladder, bowel and reproductive function is another important quality of life issue for spinal injury patients.Read moreRead less