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
Axonal Regeneration And Degeneration: Cellular And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$2,088,220.00
Summary
The ability to surgically repair an injured axon and restore neuronal function is still a significant challenge in neurosurgery. However, a spontaneous repair mechanism, axonal fusion, by which the two separated ends of a transected axon are fused back together, has been observed in invertebrates. Understanding the molecular mechanisms of this biological event will allow us to determine its potential as a novel therapeutic approach to repair injured and damaged neurons.
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.