Restoration Of The Nigrostriatal Pathway In The Parkinsonian Brain
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Many obstacles exist for cell transplantation in Parkinson's disease; namely poor restoration of the host brain circuitry due to incorrect graft placement. This results in incomplete motor function and unwanted side effects. Through iterative studies we endeavor to restore this circuitry by placing grafts in the appropriate location and promoting their survival and growth-integrations. This will require: optimizing the donor tissue and exposure of the graft to growth stimulating factors.
Wnt Signaling In Dopaminergic Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$564,721.00
Summary
A major obstacle in repairing the injured or diseased brain is inducing axons (nerve cell processes) to make the appropriate connections. This is especially true following cell replacement therapy (CRT) in Parkinson's disease (PD). We will examine the processes inducing axons in the dopamine pathways to grow. We hypothesize that Wnt signaling plays and important role and that therapeutic introduction of Wnt is required to repair the dopamine pathways following CRT in PD.
Connectivity Of Regenerating Axons Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Our objective is to thoroughly investigate the connections made by regenerating nerve fibres in mice which are treated with specific compounds to inhibit scarring as well as with active exercise following spinal cord injury. This will provide evidence of the potential of these compounds as a therapeutic intervention. Understanding how the nervous system rewires following exercise intervention will provide insights as to how new connections can be shaped to ensure optimal recovery of function.
Membrane Fusion In Axonal Regeneration: Molecules And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
Limited nerve regeneration is the main obstacle for recovery from spinal cord and brain injuries. Understanding the cellular and molecular mechanisms underlying axonal regeneration is an essential step toward the development of novel effective therapies to enhance this process. In this proposal, we use the powerful molecular and genetic tools available for the small nematode worm C. elegans to identify and study axonal regeneration and discover the key molecules involved.
Viral-mediated Modulation Of BDNF Expression In Motor Neurons To Promote The Recovery Of Hand/digits Function In A Rat Model Of Spinal Cord Injury That Impairs Normal Grasping Action.
Funder
National Health and Medical Research Council
Funding Amount
$341,427.00
Summary
This project seeks to lure injured axons towards motor neurons, a process that is essential for the recovery of motor function. BDNF gradients will be created along the injured axons path. Axons will have to elongate to reach the first source of BDNF. They will need to elongate even more to get to the next source of BDNF, hence bringing them each time closer to their lost targets. This gene therapy scenario has the potential to bring gene therapy a step closer for human spinal cord injury.
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.
Wnt Signaling In Dopaminergic Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
During development, the brain establishes intricate and precise connections. In several brain pathways, little is known about the processes regulating this connectivity. Furthermore, it is likely that the same processes will be required to repair the injured- diseased brain. This project builds on our preliminary data, that Wnt proteins are important regulators of developing dopamine pathways, and has implications for dopamine disorders including Parkinson’s disease and addiction.
Molecular And Cellular Mechanisms Of Axon Growth And Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$467,545.00
Summary
There are millions of nerve cells in the vertebrate brain, each forming very precise and specific connections within neural circuits. During development of the embryo most of these cells are wired together. A Telstra technician will use the different colours of telephone cables to correctly connect them. Likewise, the growing processes of nerve cells in the brain use specific markers or labels as cues to establish the correct wiring. The aim of the present project is to characterize the specific ....There are millions of nerve cells in the vertebrate brain, each forming very precise and specific connections within neural circuits. During development of the embryo most of these cells are wired together. A Telstra technician will use the different colours of telephone cables to correctly connect them. Likewise, the growing processes of nerve cells in the brain use specific markers or labels as cues to establish the correct wiring. The aim of the present project is to characterize the specific role of some of these labels on nerve cells during development. This project will provide new fundamental knowledge about how brain cells are wired together during development of the embryo. This knowledge is essential for establishing strategies to enhance repair of brain cells following ischemic, excitotoxic or mechanical injury.Read moreRead less
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.