Heart failure is a severely debilitating condition with a poor prognosis. It is characterized by retention of fluid and high nervous activity especially to the kidneys and the heart. Even with the best current treatment available, patients with heart failure still suffer from abnormally high nerve activity to the further detriment of this condition. The successful completion of this project will provide considerable insight into the role of the brain in the elevated nerve activity in heart failu ....Heart failure is a severely debilitating condition with a poor prognosis. It is characterized by retention of fluid and high nervous activity especially to the kidneys and the heart. Even with the best current treatment available, patients with heart failure still suffer from abnormally high nerve activity to the further detriment of this condition. The successful completion of this project will provide considerable insight into the role of the brain in the elevated nerve activity in heart failure. It will also provide us with a significant understanding of the role in reflex sympathetic nerve regulation of an important brain region known as the hypothalamic paraventricular nucleus (PVN). Our findings will help us understand the nature of the neurotransmitters contributing to the reflex nerve regulation and the specific neurons within the PVN involved. This knowledge could help us to identify novel potential therapeutic targets within the brain to alleviate the problems observed in heart failure.Read moreRead less
Determination Of Sympathetic Preganglionic Neuronal Phenotype
Funder
National Health and Medical Research Council
Funding Amount
$241,527.00
Summary
The nervous system is the single most complex part of our body. Its function depends on millions of connections between neurons, all of which must form correctly during development. Furthermore, each neuron must select a neurotransmitter with which to talk to its target neuron. A neurotransmitter is a chemical released from a neuron, which passes a signal to a target cell. Some neurotransmitters cause excitation of the target cell, others inhibition. Each neurotransmitter signals to the target c ....The nervous system is the single most complex part of our body. Its function depends on millions of connections between neurons, all of which must form correctly during development. Furthermore, each neuron must select a neurotransmitter with which to talk to its target neuron. A neurotransmitter is a chemical released from a neuron, which passes a signal to a target cell. Some neurotransmitters cause excitation of the target cell, others inhibition. Each neurotransmitter signals to the target cell via receptor molecule, matched to the neurotransmitter. Thus, a neuron is faced not only with making choices about what connections to make within the developing brain, but also it must select from a range of potential neurotransmitters and receptor molecules. We are interested in how neurons select the appropriate neurotransmitter. There are a number of ways that a neuron might be guided to the correct choice. It is possible that it could receive from the target cell a signal that guides the choice of neurotransmitter. We wish to examine this hypothesis to see if it is applicable to the autonomic nervous system, that part of the nervous system that controls functions like changes in blood pressure and heart rate. Our laboratory is expert in identifying the chemistry of autonomic neurons. We will use this knowledge to see what happens when we deliberately perturb the normal connections of autonomic neurons. Do they persist in expressing the neurotransmitters they would have done prior to the perturbation? Alternatively, do they adapt to the change of target via a signal received from the new target cell and express the appropriate phenotype? The results of these experiments will give insights into how the brain develops. The results will be important for both our basic understanding of biology and as a basis for the development of techniques for reversing neuronal damage.Read moreRead less
Roles Of Brain-derived Neurotrophic Factor In The Regulation Of Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$299,625.00
Summary
Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to ....Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to analyse physiological roles of BDNF in the brains stem and spinal cord in the regulation of nerve activity and blood pressure. The successful execution of the project will significantly enhance our understanding of how blood pressure is controlled by BDNF and nerve activity. The knowledge from this study will form basis for designing new drugs to control high blood pressure.Read moreRead less
Hypothalamic Regulation Of Cardiovascular Function In Hypertension And Stress
Funder
National Health and Medical Research Council
Funding Amount
$570,880.00
Summary
Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. The activity of sympathetic nerves is commonly increased in people with high blood pressure, particularly younger patients. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart, and increasing the risk of heart attacks and stroke. Sympathetic nerves are also activated strongly in response to stress. In ....Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. The activity of sympathetic nerves is commonly increased in people with high blood pressure, particularly younger patients. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart, and increasing the risk of heart attacks and stroke. Sympathetic nerves are also activated strongly in response to stress. In some people stress can trigger an extreme reaction, called a panic disorder, characterised by intense sympathetic activation, which also increases the risk of heart attacks. A region in the brain called the hypothalamus plays a key role in generating these increases in sympathetic nerve activity. This project aims first to identify the precise region or regions in the hypothalamus that are responsible for causing increased sympathetic activity in high blood pressure, and also in response to acute stress. There is also evidence from studies in humans that drugs which act on a particular type of receptor in the brain (called a serotonin receptor) can strongly inhibit the normal response to stress. We also aim to determine exactly where and how such drugs work. These studies may lead to much more effective treatments for high blood pressure and stress-related disorders.Read moreRead less
Neural Control Of Renal Function: Functionally Specific Populations Of Sympathetic Nerves
Funder
National Health and Medical Research Council
Funding Amount
$286,250.00
Summary
The kidneys are supplied with a dense network of nerves. Working properly, these nerves help maintain normal filtering of the blood by the kidneys. Over-activity of the nerves going to the kidney is associated with congestive heart failure, liver cirrhosis, chronic renal failure and hypertension. We have recently made several major discoveries about these nerves. Our studies suggest, based on structural and functional evidence, that stimulation of subgroups of nerve fibers going to the kidney wi ....The kidneys are supplied with a dense network of nerves. Working properly, these nerves help maintain normal filtering of the blood by the kidneys. Over-activity of the nerves going to the kidney is associated with congestive heart failure, liver cirrhosis, chronic renal failure and hypertension. We have recently made several major discoveries about these nerves. Our studies suggest, based on structural and functional evidence, that stimulation of subgroups of nerve fibers going to the kidney will causes different effects with in the kidney . We therefore suggest that salt excretion , the control of blood flow to the kidney and the release of hormones by the kidney can be seperately regulated by the nerves. Using techinques only practise in a handful of laboratories around the world, we aim to determine to how the nerves control kidney function normally. These studies will suggest new directions in which the renal nerves may be implicated in disease.Read moreRead less
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