Investigations Of Mechanisms Underlying Autonomic Cardiovascular Regulation In Medial Temporal Lobe Epilepsy.
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
People with epilepsy often show disturbed cardiovascular function which may increase mortality risk. This may reflect seizure related disturbances in the autonomic circuitry regulation of the cardiovascular system. We apply advanced brain imaging analysis of altered neural structure, circuit connectivity and function within medial temporal lobe and mid brain, combined with clinical assessment of autonomic function to provide important new insights into cardiac disturbances in epilepsy.
Investigating The Mechanisms That Increase Nerve-evoked Vasoconstriction Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$372,547.00
Summary
People with spinal cord injury not only lose control of their arms and legs but also lose control of their bladder and bowel. They also have poor control of blood pressure and an overfull bladder or bowel can lead to dangerously high blood pressure. In this project, we are investigating how this abnormal high blood pressure is generated. The aim is to develop treatments which target the mechanisms which increase the blood pressure responses elicited by the bladder and bowel.
A novel sensory neural circuit has been identified innervating the airways and lungs. The anatomical organisation of this circuit has been described to some extent in previous studies, however there is a significant gap in knowledge with respect to its functional importance. This project will develop methods to address this knowledge gap and in doing so the project will firstly describe how this circuit controls breathing under normal conditions and secondly how this becomes dysregulated during
Unravelling The Neuropathological Basis Of The Gastrointestinal Manifestations Of Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$822,957.00
Summary
Parkinson’s Disease occurs in about 1% of the population. It is a distressing, progressive disease that places a severe burden on patients, families and carers. 80-90% of Parkinson’s Disease patients have constipation which causes substantial distress to patients, their families and carers. We have a rational path to therapy for constipation of Parkinson’s Disease that will be pursued in this project
Neurogenic Diarrhoea: Lessons From Cholera Toxin And Related Bacterial Exotoxins
Funder
National Health and Medical Research Council
Funding Amount
$543,818.00
Summary
Many bacteria that cause diarrhoea act via the gut’s own nervous system to massively increase the transport of water and salt into the lumen of the intestine. In this project we will investigate mechanisms that lead to this over-excitation of the gut’s nervous system to test the idea that this is due to a change in the properties of the final nerve cells in the normal pathway that controls water transport. This will identify novel sites for drug treatments of diarrhoea.
Neural Circuits Producing Pelvic Vasodilation In Females
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
The reproductive organs and genitalia in males and females experience a large increase in blood flow during sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain. In fact, Viagra works by enhancing and prolonging the actions ....The reproductive organs and genitalia in males and females experience a large increase in blood flow during sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain. In fact, Viagra works by enhancing and prolonging the actions of these nerves. An important part of this neural pathway is a group of nerve cells in the spinal cord that connects the central nervous system with peripheral nerves in the reproductive organs - these are called preganglionic neurons. Recently we discovered that a major pathway from the spinal cord to the pelvic blood vessels in females leaves the spinal cord at a different level (lumbar) from that thought previously (sacral level). Currently there is no information on how these lumbar preganglionic nerves in females are connected to other nerve pathways that are active during sexual activity, and how they integrate signals from both the internal organs and the brain. We will use an array of modern cellular techniques together with direct observation of dilation in isolated uterine arteries to discover how these nerve cells are wired up in circuits in the spinal cord. This information is vital for us to understand the factors producing increased blood flow in normal sexual activity, and how these might be altered in inflammation or in conditions where there could be selective damage to one nerve pathway and not the other, such as after pelvic surgery, spinal cord damage at different levels, or stimulation of the spinal cord for treatment of chronic pain. Our study also will help understand referred pain and sensations of discomfort in abdominal and pelvic organs.Read moreRead less
Currents That Set The Excitability Of Enteric Neurons And Their Roles At Cell And Organ Levels
Funder
National Health and Medical Research Council
Funding Amount
$459,014.00
Summary
The intestine is subject to a number of disorders of its normal control by nerves, including diarrhoea, constipation and slow transit disorders. Chronic and debilitating derangement of intestinal function occurs in irritable bowel syndrome, which affects around 10-15% of people in our community, about 1% at any one time. Irritable bowel syndrome can persist for many years, and there is no adequate therapy. For some patients no medication gives relief, and for most the relief is minimal. The refl ....The intestine is subject to a number of disorders of its normal control by nerves, including diarrhoea, constipation and slow transit disorders. Chronic and debilitating derangement of intestinal function occurs in irritable bowel syndrome, which affects around 10-15% of people in our community, about 1% at any one time. Irritable bowel syndrome can persist for many years, and there is no adequate therapy. For some patients no medication gives relief, and for most the relief is minimal. The reflexes in the intestine that control its movements and secretion depend for their initiation on a special type of neuron, known as the intrinsic primary afferent neuron. These neurons have properties that determine how active they are. These properties distinguish them from all other enteric neurons. If the activity of intrinsic primary afferent neurons is controlled, then the intensity and character of enteric reflexes are also controlled. Thus it is feasible to target molecules in these neurons that could be used to treat constipation or diarrhoea, or to accelerate movement of food along the intestine. Our work has identified molecular targets and some of the medicinal compounds that could be useful to patients. The project will further define the molecular targets, determine the specificity of potential treatments and test the effectiveness of the medicinal compounds in an animal model.Read moreRead less
Regeneration Of Pelvic Autonomic Axons After Injury
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
This project is focused on the problem of erectile dysfunction, especially the common situation where this is caused by injury to the penile nerves. These nerves are part of the parasympathetic nervous system . Nerve injury-induced erectile dysfunction is a common problem for prostatectomy patients, with recovery of normal erections occurring slowly, partially or not at all. There is currently no therapy to improve regeneration of these nerves, and this is partly because very little is known abo ....This project is focused on the problem of erectile dysfunction, especially the common situation where this is caused by injury to the penile nerves. These nerves are part of the parasympathetic nervous system . Nerve injury-induced erectile dysfunction is a common problem for prostatectomy patients, with recovery of normal erections occurring slowly, partially or not at all. There is currently no therapy to improve regeneration of these nerves, and this is partly because very little is known about effects of injury on any parasympathetic neurons, and especially for those that are essential for erection. The first aim of this study is to define the key structural and functional changes occurring in penile parasympathetic neurons during regeneration after injury. This fundamental neurobiological knowledge is essential to develop and optimise an future growth treatments. The second aim of the study is to define the effects of a protein, neurturin, on axonal regeneration of penile pro-erectile neurons. Our evidence so far strongly suggests that it is necessary for the early stages of injury responses. Our studies will be performed in mice, where we also have colonies of knockout animals to study the effect of removing neurturin from the regeneration process. Our experiments will include neuroanatomical studies of injured and growing nerves, pharmacology studies on penile smooth muscle (corpus cavernosum) innervation and responsiveness, and tissue culture studies. We will investigate not only the changes that occur following injury to penile nerves, but also the way in which undamaged nerves may assist in returning erectile function.Read moreRead less