Vasomotor Ganglionic Transmission: The Preganglionic Peptide And The Second Gear
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Blood pressure depends on nerve signals that travel from the central nervous system to blood vessels. In the middle of this pathway is a relay station - the sympathetic ganglion cell. Transmission through this relay station has recently been shown to have not only a fixed but also a variable component - the 'second gear'. The project tests if and how three likely candidate peptide molecules, one in the nerves, two in the bloodstream, control this 'second gear' and hence regulate blood pressure.
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.
Postviral Wheezing In Childhood: Disregulation Of Airway Tone?
Funder
National Health and Medical Research Council
Funding Amount
$577,040.00
Summary
Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. Ho ....Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. However, many infants who wheeze with viral infections, especially in the first year of life, do not develop allergies in later life, raising the possibility that they did not have the same type of asthma as those whose symptoms persist. This project will study the effects of viral infections on lung function to determine whether particular types of virus can have detrimental effects of lung function lasting for years. We will also examine whether the age at which the infection occurs and the severity of the infection influence the long-term outcome. The project involves studying infants during the recovery phase of respiratory viral infections, older children years after documented infections and experimental animal models that have been infected under controlled conditions. By determining whether respiratory viral infections can have long-term effects on lung function that can mimic asthma, we will advance our understanding of how asthma develops. In addition, specific treatment and preventative strategies could then be developed to prevent these long-term abnormalities, instead of relying on asthma medication (especially inhaled corticosteroids) as is the current practice. Preventative strategies could include encouraging the development of specific vaccines.Read moreRead less
Sjogren's Syndrome As A Disorder Of Anti-receptor Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
A new approach to understanding Sjogren's syndrome Sjogren's syndrome (SS) is a frequent cause of illness predominantly in women, leading to frequent attendances to medical, dental and allied health practitioners. Historically considered a rarity, SS, in both its primary and secondary forms, is arguably the commonest manifestation of human systemic autoimmunity. Increasingly recognised by clinicians as the unifying diagnosis underlying a plethora of chronic disabling symptoms in women from the f ....A new approach to understanding Sjogren's syndrome Sjogren's syndrome (SS) is a frequent cause of illness predominantly in women, leading to frequent attendances to medical, dental and allied health practitioners. Historically considered a rarity, SS, in both its primary and secondary forms, is arguably the commonest manifestation of human systemic autoimmunity. Increasingly recognised by clinicians as the unifying diagnosis underlying a plethora of chronic disabling symptoms in women from the fourth decade and beyond, therapeutic options remain limited due to our primitive understanding of its cause. Emerging evidence suggests that rather than a consequence of physical destruction of salivary and tear glands by cells of the immune system, severe dryness of the mouth and eyes in SS might be caused by antibodies which block the transmission of signals from tiny nerves to receptors in these glands. We also have evidence that other symptoms experienced by patients with SS, including abnormal sweating, irritable bladder and bowel, and Raynaud's phenomenon, may also be the consequence of blockage of nerve supply. Furthermore, we have detected these blocking antibodies in patients with both primary SS and rheumatoid arthritis accompanied by secondary SS, pointing for the first time to a common underlying cause for SS in these two settings. We propose a new approach to understanding Sjogren's syndrome, as a disease of anti-receptor autoimmunity, akin to Graves disease of the thyroid gland. This opens up exciting possibilities for the development of new techniques for the diagnosis and treatment of SS.Read moreRead less
Roles Of The Peptide Hormone, Ghrelin, In The Spinal Cord
Funder
National Health and Medical Research Council
Funding Amount
$414,326.00
Summary
This study investigates the control of internal organs of the body, the heart, blood vessels, intestine and bladder. We have made the new and surprising discovery that ghrelin, previously known to be a hormone, is probably also a neurotransmitter in the spinal cord. This raises the possibility that drugs that act on ghrelin receptors in the spinal cord could be used to treat high blood pressure or other problems of internal organs.
Cysteine-rich Secretory Protein Regulation Of Ion Channels In Male Fertility And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$474,309.00
Summary
Diagnosis of the precise causes of male infertility and the development of male contraceptives requires improved understanding of sperm function. The Cysteine-Rich Secretory Proteins (CRISPs) are produced in the male reproductive tract where they regulate sperm function. Our project will demonstrate the essential requirement for CRISPs in sperm function and investigate their role in other tissues of the reproductive tract, including the prostate where they may be involved in prostate cancer.
What Triggers Complex Regional Pain Syndrome After Minor Injury?
Funder
National Health and Medical Research Council
Funding Amount
$958,898.00
Summary
Most people recover from minor trauma but some develop very disabling, difficult to treat, costly pain syndromes. We can identify those at high risk of developing such a syndrome after wrist fracture. By comparing inflammation, immune system function, stress, brain function and behaviour between high and low risk patients, we will take a major step towards understanding, preventing and treating these syndromes.
Cysteine Rich Secretory Proteins (Crisp) Are Ion Channel Regulators With Essential Roles In Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
Male infertility affects 1 in 20 Australian men and for the majority of other men, contraception is an issue at some point in their lives. Despite this, relatively little is known about the processes of sperm production and fertilization. As such, there is an urgent need for futher research if we are to hope to develop diagnostics, targeted therapeutics and to take advantage of the growing awareness by pharmaceutical companies of the market for male gamete based contraceptives. The cysteine rich ....Male infertility affects 1 in 20 Australian men and for the majority of other men, contraception is an issue at some point in their lives. Despite this, relatively little is known about the processes of sperm production and fertilization. As such, there is an urgent need for futher research if we are to hope to develop diagnostics, targeted therapeutics and to take advantage of the growing awareness by pharmaceutical companies of the market for male gamete based contraceptives. The cysteine rich secretory proteins (Crisps) are a group of proteins which show a remarkable bias to the male reproductive tract. All four are incorporated into sperm. Recently published data from us indicates that they have the ability to regulated calcium flow in sperm and as such sperm activity. The aim of the current proposal is to explore the biological relevance of one domain of Crisp proteins using animal models, in vitro sperm tests and through an analysis of ion flux and phosphorylation status under conditions of altered Crisp-1 and -2 content. The data generated from this project will make a significant contribution to the development of novel male gamete based contraceptives for use by either men or women. In addition, through the attainment of a greater understanding of sperm development and function, we will be able to more precisely define types of infertility, thus allowing for the development of more targeted therapies. The development of Crisp agonists or antagonists may also be of value in the treatment of other cilia disorders including primary cilia dykinesia and cystic fibrosis.Read moreRead less
PREMOTOR SYMPATHETIC CONTROL OF BLOOD PRESSURE DURING PSYCHOLOGICAL STRESS: HYPOTHALAMUS VERSUS MEDULLA.
Funder
National Health and Medical Research Council
Funding Amount
$153,616.00
Summary
Health and well being depend in large part on a strong and efficient autonomic nervous system. The autonomic nervous system controls blood pressure, heart rate, gastrointestinal function, immune responses and certain forms of pain. Negative emotions can have a strong impact on autonomic function. We have all experienced the sweaty hands, pounding heart and intestinal discomfort when the mail arrives and bad news is expected or when we face a deadline for which we are not prepared. This is known ....Health and well being depend in large part on a strong and efficient autonomic nervous system. The autonomic nervous system controls blood pressure, heart rate, gastrointestinal function, immune responses and certain forms of pain. Negative emotions can have a strong impact on autonomic function. We have all experienced the sweaty hands, pounding heart and intestinal discomfort when the mail arrives and bad news is expected or when we face a deadline for which we are not prepared. This is known as psychological stress and it is usually associated with anxiety. Unfortunately, it is also the most common form of stress in modern urban life. There are clear indications that when these autonomic changes become chronic they can lead to hypertension, weak immune responses and gastric ulcers. In people already suffering from cardiovascular diseases they can also precipitate cardiac and cerebrovascular accidents. Clearly, the link between psychological stress and the autonomic nervous system needs to be explored in more detail. This project looks at the organization of the neural network in the brain and spinal cord that controls these responses. It uses a simple model of psychological stress in the conscious rat and recent non invasive techniques to record blood pressure and look at neuronal activity. We think that we have identified a group of neurons that may be controlling very specifically this response. It is located in the hypothalamus. The aim of this project is to further test the role of these neurons and find out what is controlling them. They will also be compared to another group of neurons that also controls blood pressure but apparently not in relation to psychological stress. The possibility that the cardiovascular response to psychological stress might be mediated by a specific group of neurons in the brain is a very exciting finding. It could lead to new therapeutic applications for acting against the short and long term effects of stress.Read moreRead less
Inhibition Of Fear Memories By Extinction: Neural Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$234,250.00
Summary
Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relati ....Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relatively little is known about the mechanisms by which fear memories can be inhibited or suppressed. Understanding this latter process is a key to the development of effective treatments for anxiety disorders such as PTSD where the patient suffers from persistent, intrusive, unwanted trauma memories. A common experimental procedure for reducing learned fear is to repeatedly expose the subject to a fear-eliciting stimulus but without any aversive outcome. This procedure leads to a progressive loss, or extinction, of the fear reactions elicited by the stimulus. Historically, the extinction of fear was thought to be due to an erasure of the fear memory. However, recent evidence shows that extinction inhibits, rather than erases, the fear memory. Because the fear memories remain intact, some structure(s) in the brain must inhibit activity in the fear pathway. This project uses extinction of conditioned fear reactions in rat subjects to determine the structure(s) in the brain that inhibit fear memories and their behavioural and cardiovascular expression. It brings together the expertise of four well-established researchers and uses a combination of behavioural, physiological, immunohistochemical, tract tracing, and lesion approaches to achieve this aim. The proposed experiments will reveal the structure(s) in the brain that control the inhibition of fear, as well as the site(s) of this inhibition in the fear pathwayRead moreRead less