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How Does The LRP Receptor Megalin Promote Regenerative Neuronal Growth?
Funder
National Health and Medical Research Council
Funding Amount
$408,739.00
Summary
Promoting the regenerative growth of neurons to allow recovery from traumatic brain injury or Alzheimer's disease is a major goal of neuroscientists. This project continues the Chief Investigators' work in which they have discovered the regenerative potential of a protein and focuses on how this protein interacts with a key neuronal receptor, megalin, which appears to drive the regenerative process. This work will identify new targets for therapies for a range of nervous system disorders.
Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can ....There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can be used to assist in trying to modulate and facilitate directed regrowth following injury.Read moreRead less
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.
Roles Of Brain-derived Neurotrophic Factor In Plasticity Of Injured Sensory Neurons
Funder
National Health and Medical Research Council
Funding Amount
$461,443.00
Summary
The fundamental problem of how nerve cells respond to a nerve injury has long been studied by neuroscientists and clinicians. After a nerve injury outside the brain or spinal cord, ie, in the periphery, some sensory nerve cells die, some regenerate to reconnect to their targets, and some sprout to make abnormal connections. Recent evidence from our lab and others indicates that the nerve sprouting is linked to chronic pain experienced by nerve-injury patients. However, how these changes occur st ....The fundamental problem of how nerve cells respond to a nerve injury has long been studied by neuroscientists and clinicians. After a nerve injury outside the brain or spinal cord, ie, in the periphery, some sensory nerve cells die, some regenerate to reconnect to their targets, and some sprout to make abnormal connections. Recent evidence from our lab and others indicates that the nerve sprouting is linked to chronic pain experienced by nerve-injury patients. However, how these changes occur still remains largely unknown. Our recent studies showed that growth factors, particularly brain-derived neurotrophic factor (BDNF) which is made by the sensory nerve cells, may play important roles in mediating these changes. This proposed project, directly evolved from our recent exciting findings, aims to further examine roles and action mechanisms of BDNF and its relatives in regulating the responses of sensory nerve cells to a nerve injury. We propose that after an injury, BDNF promotes survival of some nerve cells, enhances sensory nerve regeneration in both periphery and spinal cord, and also mediates abnormal nerve sprouting and is involved in neuropathic pain. With strong expertise and powerful tools in hand, we have designed a series of experiments to investigate the roles and action mechanisms of BDNF and its related molecules in these processes. Results from this project will help us understand mechanisms underlying the responses of nerve cells to a nerve injury, and should provide much needed information which would help in designing new methods for enhancing nerve cell survival and nerve regeneration as well as for inhibiting nerve injury-induced chronic pain in nerve-injury patients.Read moreRead less
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
Modulation Of Calcium Signalling By Acetylcholine In The Basolateral Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$266,748.00
Summary
The amygdala is an area of the brain involved in assigning emotional significance to sensory stimuli. This grant examines the cellular processes involved in making these associations. Specifically, it studies the relationship between two signalling molecules implicated in association learning, acetylcholine and calcium. This research will test hypotheses of memory formation and provide insight into disorders linked to detrimental emotional associations, such as anxiety and addiction.
Modulation And Trafficking Of SK Channels In The Lateral Amygdala
Funder
National Health and Medical Research Council
Funding Amount
$260,980.00
Summary
The amygdala is a brain structure that underlies emotional processing. Malfunctions in emotional processing are thought to be the cause of anxiety disorders. Understanding amygdala physiology is thus vital for developing therapies to treat these disorders. We have recently found a novel role for an ion channel in controlling amygdala excitability. In this grant we will investigate how this ion channel is modulated, which will elucidate a novel way in which activity in the amygdala is regulated.
Prof Paxinos ‘s work is involved in understanding brain organisation and function through the fusion of the fields of molecular genetics, comparative and developmental neuroanatomy and Neuro informatics
Role Of ABCA-G Transporters In Neuronal Cholesterol Regulation And Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$557,582.00
Summary
Alzheimer's disease (AD) prevalence is rising and the contributing factors are poorly understood. Recent research shows that cholesterol regulates the production of neurotoxic amyloid-beta peptide (Abeta). We will study a class of proteins, ABC transporters, that we believe regulate neuronal cholesterol and Abeta metabolism. We will use isolated brain cells, human brain tissue and genetically engineered mice in order to define how cholesterol influences AD and identify new treatment options.