How Amyloid Causes Neurodegeneration: The Role Of Transthyretin In Familial Amyloidotic Polyneuropathy
Funder
National Health and Medical Research Council
Funding Amount
$618,950.00
Summary
This project seeks to understand the biochemical basis of nerve degeneration in a disease known as familial amyloidotic polyneuropathy. This disease is caused by a protein known as transthyretin, which is abnormally deposited around nerves and causes nerve damage. The project is highly likely to provide clues which help us understand some related dementia causing diseases like Alzheimer's disease and prion diseases such as scrapie and mad cow disease.
Nerve pathways exist that carry information from the highest parts of the brain to the peripheral hearing organ, the inner ear. These descending control pathways have the potential to affect the hearing process in a number of ways; protecting from loud sounds, improving the detection of signals in noisy backgrounds, selecting stimuli of interest and regulating a variety of aspects of inner ear function. Abnormal function of these pathways can affect hearing sensitivity and may be important in ph ....Nerve pathways exist that carry information from the highest parts of the brain to the peripheral hearing organ, the inner ear. These descending control pathways have the potential to affect the hearing process in a number of ways; protecting from loud sounds, improving the detection of signals in noisy backgrounds, selecting stimuli of interest and regulating a variety of aspects of inner ear function. Abnormal function of these pathways can affect hearing sensitivity and may be important in phenomena such as tinnitus and other disorders of hearing. This project will investigate the subtle effects that selective activation of these pathways has on inner ear function and will attempt to unravel the different influences that subcomponents of the pathways have on the different aspects of hearing.Read moreRead less
Do Postjunctional Alterations Explain The Effects Of Diabetes On Neurovascular Transmission?
Funder
National Health and Medical Research Council
Funding Amount
$390,886.00
Summary
Diabetes produces disordered skin blood flow that increases risk of skin ulcers and gangrene. The project investigates nervous control of skin blood vessels in diabetes. It is assumed that all affects of diabetes on nerve function are explained by loss of nerves. We hypothesize that some affects of diabetes are due to dysfunction of blood vessels and not to nerve loss. The objective is to identify drug targets to improve blood flow in skin and thereby reduce the risk of skin ulcers and gangrene.
Anti-viral Immunity And The Survival Of Cells Infected With Herpes Simplex Virus In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Herpes simplex virus causes cold sores and genital herpes. A person can only catch the virus once in their life, but it stays in their body and can cause occasional outbreaks of disease. This recurrent disease can be frequent and severe. The place where the herpes virus hides in a dormant state between outbreaks is in the nervous system. This project aims to learn more about how the virus becomes dormant and also whether the immune system is important in keeping the virus in this state.
Segmentation Of The Peripheral Nervous System - The Role Of Axon Guidance Factors.
Funder
National Health and Medical Research Council
Funding Amount
$190,331.00
Summary
Injury to the nervous system results in great loss to the individual and society at large. To repair a damaged nerve pathway so that functional recovery may ensue is the pre-eminent goal of neuroscience research. An understanding of how factors that guide nerve processes coordinate the wiring of the nervous system during development of an embryo will provide an insight into what strategy is required to repair a damaged nerve pathway in the mature nervous system. In this research project we propo ....Injury to the nervous system results in great loss to the individual and society at large. To repair a damaged nerve pathway so that functional recovery may ensue is the pre-eminent goal of neuroscience research. An understanding of how factors that guide nerve processes coordinate the wiring of the nervous system during development of an embryo will provide an insight into what strategy is required to repair a damaged nerve pathway in the mature nervous system. In this research project we propose to investigate what factors guide the formation of the peripheral nervous system which controls the body. We will use a novel model system whereby a whole chick embryo is grown in a culture dish and the developing nerve pathways can be manipulated to discover what are the exact factors that guide nerve processes to wire up pathways to the limbs and other body parts. This research will provide an opportunity to study the basic principles of nerve pathfinding which may then be applied to more complicated circuits within the brain and to the repair of injured nerve pathways.Read moreRead less
Intrauterine Growth Restriction And Development Of The Peripheral And Coronary Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$437,176.00
Summary
There have been no studies which have investigated the extent to which fetal substrate restriction and associated fetal growth restriction alter the expression of nerve growth factors which determine the extent of sympathetic innervation of the peripheral vasculature and the interaction of changes within the peripheral and coronary vasculature which may explain the association between fetal growth restriction and the emergence of cardiovascular disease and high blood pressure in later life. Thes ....There have been no studies which have investigated the extent to which fetal substrate restriction and associated fetal growth restriction alter the expression of nerve growth factors which determine the extent of sympathetic innervation of the peripheral vasculature and the interaction of changes within the peripheral and coronary vasculature which may explain the association between fetal growth restriction and the emergence of cardiovascular disease and high blood pressure in later life. These studies ill provide new insights into the lifelong cardiovascular sequelae of a suboptimal intrauterine environment.Read moreRead less
Modulation Of Autonomic Nerve Growth By Guidance Factors
Funder
National Health and Medical Research Council
Funding Amount
$393,277.00
Summary
Our goal is to understand how adult nerves are affected by injury so that we can devise therapies to make them regrow better. We will focus on nerves that control the urogenital organs because these are often injured during surgical procedures (e.g. prostatectomy, hysterectomy), with devastating effects on patients' quality of life. In this project we will investigate how naturally-occurring growth-inhibitory molecules affect nerve regrowth after injury in the pelvic nervous system.
Involvement Of Adrenergic Receptors In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$345,473.00
Summary
After nerve or tissue injury including burns, some people will suffer from a condition called neuropathic pain. This is a condition where chronic pain is endured, often totally unrelated to the initial injury or induced by events that would normally not be painful. Our project will determine whether this abnormal pain response is due to an abnormal communication between the nerves that carry pain signals (sensory nerves) and nerves that form part of the sympathetic nervous system, which is part ....After nerve or tissue injury including burns, some people will suffer from a condition called neuropathic pain. This is a condition where chronic pain is endured, often totally unrelated to the initial injury or induced by events that would normally not be painful. Our project will determine whether this abnormal pain response is due to an abnormal communication between the nerves that carry pain signals (sensory nerves) and nerves that form part of the sympathetic nervous system, which is part of autonomic (or involuntary) nervous system. We believe that this abnormal communication is due to an increase in the expression of special receptors called adrenergic receptors, on the sensory nerves. Our project will look at these receptors in the skin of animals that have had pain conditions induced, and also in skin samples from patients who suffer from neuropathic pain that can be classified as sensitive to sympathetic stimulation. By better understanding how neuropathic pain is derived, we can open the door to novel treatment approaches in these difficult to treat conditions.Read moreRead less
Understanding the biological mechanisms of nerve degeneration is an essential step toward the development of novel therapies for human neurodegenerative conditions such as Parkinson's, Alzheimer's and Huntington's diseases, and for spinal cord injuries. The studies presented in this proposal, using the powerful molecular and genetic tools available for the small nematode worm C. elegans, will provide new insights into the cellular and molecular mechanisms responsible for nerve degeneration.
Role Of The Hypothalamus, Oxidative Stress And Angiotensin In Chronic Stress
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Stress can trigger life threatening cardiovascular events and its impact is much greater when blood pressure is raised. We seek to determine which chemical type of brain neuron and which region is responsible for amplifying the responses to repeated stress in an animal model that closely resembles the human form of the disease. We will focus specifically on the hypothalamus which controls the sympathetic nervous system.