I am a neurophysiologist interested in brain regulation of homeostatic and autonomic functions in health and disease. I am endeavouring to discover the brain pathways for these vital functions, and to translate my findings from animal research to humans.
Neural Mechanisms Mediating Inhibitory Influences Of Hyperthermia, Fever And Age On Water Intake
Funder
National Health and Medical Research Council
Funding Amount
$324,125.00
Summary
An adequate intake of fluid following losses of body water that can occur as the result of sweating in hot weather, exercise, vomiting or diarrhoea is necessary so that dangerous levels of dehydration do not occur. Thus, it is important for our health that thirst is properly stimulated when we do become dehydrated, in order that we are aware that we must drink water. There may be conditions in which the thirst mechanism is inhibited, and the aim of these experiments is to identify and understand ....An adequate intake of fluid following losses of body water that can occur as the result of sweating in hot weather, exercise, vomiting or diarrhoea is necessary so that dangerous levels of dehydration do not occur. Thus, it is important for our health that thirst is properly stimulated when we do become dehydrated, in order that we are aware that we must drink water. There may be conditions in which the thirst mechanism is inhibited, and the aim of these experiments is to identify and understand mechanisms by which the thirst mechanism in the brain is supressed. We have observed that a high body temperature may have an inhibitory influence on thirst in rats, and it is also known that thirst mechanisms are depressed in elderly people. If we can identify the regions of the brain that are involved and the mechanisms underpinning this reduced thirst, then it will be possible to identify and alert people at risk and to design strategies to prevent dangerous levels of dehydration occurring due to reduced thirst, particularly in the elderly. This may also apply to to people who may be working or undertaking vigorous exercise in hot weather or taking certain medications.Read moreRead less
Does Early Overnutrition Differentially Alter Hypothalamic Neuropeptides That Regulate Food Intake In The Rat
Funder
National Health and Medical Research Council
Funding Amount
$346,250.00
Summary
In Australia the incidence of obesity, in particular childhood obesity, is increasing dramatically, and the possible long term consequences of this are of great concern. The brain regulates appetite through a number of chemical transmitters such as neuropeptide Y (NPY) which is present in the brains of mammals and causes increased food intake. The effects of overeating from a young age on these brain transmitters has been largely ignored although this may impact on subsequent eating behaviour. I ....In Australia the incidence of obesity, in particular childhood obesity, is increasing dramatically, and the possible long term consequences of this are of great concern. The brain regulates appetite through a number of chemical transmitters such as neuropeptide Y (NPY) which is present in the brains of mammals and causes increased food intake. The effects of overeating from a young age on these brain transmitters has been largely ignored although this may impact on subsequent eating behaviour. In addition to NPY we will study other transmitters in the brain that have profound effects on appetite, some increasing, and others decreasing, food intake. These may form useful therapeutic targets for new drugs for obesity. Key targets we will study include melanocortins, glucagon-like peptide 1, urocortin, melanin concentrating hormone, agouti related peptide, and NPY. We will determine whether overnutrition from birth to weaning leads to changes in these appetite regulating neurotransmitters in the brain, and monitor the hormonal signals that impact on their activity. We will also determine whether early overnutrition exacerbates the subsequent responses to a high fat diet by comparison with rats made obese as adults. We will measure brain concentrations of the neurotransmitters, the amount released from the brain, and determine whether the feeding responses to injections of these agents is altered in obese animals. We have evidence that these transmitters interact in a co-ordinated fashion to affect feeding; this project will examine whether these interactions are maintained in the various types of obesity. Rats are commonly used for this type of study as the processes regulating feeding are very similar to those in humans and these agents cause similar effects in rats and humans. It is hoped that this information will provide new insight into the way brain adapts to overnutrition, and provide potential treatments for obesity and other feeding disorders.Read moreRead less
Influences Of Oestrogen On Neurodegeneration And Behaviours
Funder
National Health and Medical Research Council
Funding Amount
$620,352.00
Summary
More women develop Alzheimer's disease whereas more men develop Parkinson's disease. This study will try to understand whether sex hormones play a part in the devlopment of these diseases. This study will also try to answer how the female sex hormone, oestrogen, influences behaviour and or development of mental health problems such as depression and obsessive-compulsive disorder.
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
Forebrain Control Of Cardiovascular Function: Integrative And Cellular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$834,233.00
Summary
Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. Measurements in humans have shown that the activity of sympathetic nerves is increased in a number of cardiovascular diseases, including heart failure and in many cases of high blood pressure. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart which can cause damage to the heart. It is not known what ....Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. Measurements in humans have shown that the activity of sympathetic nerves is increased in a number of cardiovascular diseases, including heart failure and in many cases of high blood pressure. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart which can cause damage to the heart. It is not known what causes this increased sympathetic activity, but one possibility is that it is due to the action of a circulating hormone called angiotensin, which acts on the brain, activating central nerve pathways which ultimately increase sympathetic activity. In this project we aim to test this hypothesis and thus help to unravel the mechanisms involved in the long term control of sympathetic activity and blood pressure.Read moreRead less
Human Hypothalamic Homologues To Autonomic Control Centres Identified In Rat And Monkey
Funder
National Health and Medical Research Council
Funding Amount
$358,770.00
Summary
The hypothalamus is a brain structure common to all mammals. Experiments on the rat have shown the hypothalamus to be fundamentally involved in cardiovascular control, fluid and electrolyte balance, food ingestion and energy metabolism, thermoregulatory and immune responses, and defensive-aggressive responses and reproduction. It is virtually impossible to perform functional studies in the human and, therefore, the human hypothalamic regions involved in these functions will be inferred from thei ....The hypothalamus is a brain structure common to all mammals. Experiments on the rat have shown the hypothalamus to be fundamentally involved in cardiovascular control, fluid and electrolyte balance, food ingestion and energy metabolism, thermoregulatory and immune responses, and defensive-aggressive responses and reproduction. It is virtually impossible to perform functional studies in the human and, therefore, the human hypothalamic regions involved in these functions will be inferred from their structural similarity to the centres identified in the rat. The present project will obtain structural-chemical data on the rat and monkey for the sole purpose of comparing these data with similar data on the human. The parts of the hypothalamus that deal with cardiovascular and other autonomic functions are expected to be similar in the rat and human and the present study will identify in the human all major regions that have been identified in the rat. The correspondence between an area in the rat brain and one in the human brain will be established primarily on the basis of chemical similarity. Corresponding areas tend to feature similar neurotransmitters, enzymes and other neuroactive substances. Some of the chemicals to be investigated are known to have a role in autonomic control. The chemical mapping study then serves two roles: (a) It permits the identification of the chemical profile (signature) of an area and consequently enables its identification in the human, and (b) it reveals the chemicals the area utilizes for possible theoretical and practical considerations. The present study will allow hypotheses derived from experimental work on the rat to be more meaningfully tested on humans. It will assist pathological and imaging investigations of the human brain.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