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How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
Brain Control Of The Thermoregulatory Cutaneous Circulation: A Window To The Mind, And To The Neurobiology Of Clozapine
Funder
National Health and Medical Research Council
Funding Amount
$561,396.00
Summary
Patients suffering from schizophrenia benefit from medication. Discovering the brain mechanisms whereby the medications work is most important. Action of many important drugs have been established in experimental animals. This is a difficult task for anti-schizophrenia drugs because it is difficult to establish what animals are thinking or feeling, and it is doubtful whether animals ever suffer from schizophrenia. Thus it would be very advantageous to discover a physiological response, measurabl ....Patients suffering from schizophrenia benefit from medication. Discovering the brain mechanisms whereby the medications work is most important. Action of many important drugs have been established in experimental animals. This is a difficult task for anti-schizophrenia drugs because it is difficult to establish what animals are thinking or feeling, and it is doubtful whether animals ever suffer from schizophrenia. Thus it would be very advantageous to discover a physiological response, measurable in, for example, rats, that can serve as a marker of the animal s emotional responses to situations that would normally prove anxiety-provoking. The present grant is based on the discovery, in my laboratory, that stressful stimuli cause sudden falls in blood flow to the tail in rats. My laboratory is the first in the world to measure pulsatile blood flow to the tail in conscious rats, and this is why we made our discovery. My laboratory also discovered that clozapine, a drug of major theoretical and practical importance for the treatment of schizophrenia inhibits fright-induced constriction of the tail artery. Clozapine interacts with many potential neurotransmitters in the brain. Some very complex combinations of these interactions are presumably responsible for the drug s unique psychotherapeutic action in schizophrenia. Our discovery that clozapine inhibits fright-induced constriction of the tail artery means that we will be able to investigate clozapine s mechanisms of action. Results of our findings are genuinely likely to increase our understanding of how clozapine works in schizophrenia. This information should also provide clues as to the nature of the presently mysterious brain malfunctions that result in schizophrenia.Read moreRead less
Cardiovascular Reactivity To Stress: Role Of Redox Signalling In The Hypothalamus And Brainstem
Funder
National Health and Medical Research Council
Funding Amount
$606,979.00
Summary
Cardiovascular disease is Australia's greatest health problem. It kills more people than any other disease and affected 3.5 million Australians in 2004-05. More and more evidence suggests a relationship between the risk of cardiovascular disease and mental stress. But more research is needed on how stress contributes to heart disease risk. This project aims to determine the role of harmful molecules, called free oxygen radicals, in brain in mediating effects of stress on cardiovascular system.
Influence Of Superoxide On The Central Cardiovascular Response To Emotional Stress: Cellular And Subcellular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$642,599.00
Summary
Cardiovascular disease is Australia's greatest health problem. It kills more people than any other disease and affected 3.5 million Australians in 2004-05. More and more evidence suggests a relationship between the risk of cardiovascular disease and mental stress. But more research is needed on how stress contributes to heart disease risk. This project aims to determine the role of harmful molecules, called free oxygen radicals, in brain in mediating effects of stress on cardiovascular system.
Central Regulation Of Blood Pressure : Role Of Angiotensin And Nitric Oxide
Funder
National Health and Medical Research Council
Funding Amount
$488,250.00
Summary
High blood pressure is a major public health problem in Western society with approximately 20% of adults affected. If left untreated serious damage to organs can occur and the risk of sudden cardiac death or stroke is greatly increased. While many factors contribute to the development of hypertension such as lifestyles, genes, diet, weight and exercise levels, a common feature in the early stages is an overactive nervous system in the kidney and in the heart which is most likely due to altered s ....High blood pressure is a major public health problem in Western society with approximately 20% of adults affected. If left untreated serious damage to organs can occur and the risk of sudden cardiac death or stroke is greatly increased. While many factors contribute to the development of hypertension such as lifestyles, genes, diet, weight and exercise levels, a common feature in the early stages is an overactive nervous system in the kidney and in the heart which is most likely due to altered signals from the brain. A major question has been to understand why this occurs. One possibility is angiotensin (a hormone released from the kidney that is known to control body fluid) also acts in the brain to increase nerve activity to the kidney and heart and in this way contribute to high blood pressure. Our research has shown that normally brain angiotensin has relatively little activity but can be switched on by specific situations such as stress or a high salt. This may be by depleting anti-oxidants and producing an oxidative stress in the brain. With aging, stress, lack of exercise and other various environmental influences our body is less able to cope with oxidative stress which is the result of the normal cells function. The major thrust of this project is to determine whether the long term contribution of angiotensin in the brain to high blood pressure is caused by a high level of oxidative stress in the brain. We will see whether experimental animals still develop high blood pressure if angiotensin is blocked in the brain and see whether changing the oxidative stress levels in the brain affects this role. We will be able to better understand the interplay between these molecules in the brain which opens the way for the development of new highly specific drugs that can prevent the high level of nerve activity to the heart and kidney and hence the development of high blood pressure.Read moreRead less
The Amygdala And Emotionally-mediated Sudden Cutaneous Vasoconstriction In Rats
Funder
National Health and Medical Research Council
Funding Amount
$461,788.00
Summary
Discovering how the brain organizes our emotional life is important for understanding mental illness. In rats, blood flow to the skin falls when the animal detects a possibly dangerous event. Rats go pale with fright , just as humans do. The falls in blood flow are inhibited by drugs used to treat people with schizophrenia. The grant investigates whether the amygdala is an important brain centre controlling the skin blood vessels, and whether anti-schizophrenia drugs act in the amygdala.
How well people perform in everyday situations is often determined by memory function. When required to perform under stress memory performance is often affected. The effect of a psychological stress test on memory function in healthy volunteers and the ability of a dietary supplement, tyrosine, to prevent the effects will be studied. The data may suggest that depletion amino acids is responsible for the decrements in performance that are evident after an acute stressor.
I have discovered particular factors produced by our white blood cells have the ability to shut down or boost protein production in the gut, pancreas and lung. My vision is to harness these to devise new strategies for treatments for infectious and non-infectious diseases (inflammatory bowel disease, diabetes) that have a high burden on our healthcare system.
Central Control Of Stress-induced Changes In Immune Function.
Funder
National Health and Medical Research Council
Funding Amount
$411,724.00
Summary
LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol ....LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol in our body is beneficial because it can prevent the infection from taking hold in our body and spreading. However if we are chronically stressed our brains tell the adrenal glands to secrete excessive amounts of cortisol over long periods of time and this imbalance can actually hinder the ability of one's immune system to fight an infection. The unfortunate consequence is that the infection is more likely to win the battle and spread to cause further havoc. The present study will identify which areas of the brain are important in driving the secretion of cortisol during infection and how long-term stress can influence those areas. Because we might be exposed to long-term psychological stress that is repeated regularly or irregularly we will determine which pattern of stress has the greatest effect. An investigation into how the brain operates during long-term stress and infection will help us develop ways to prevent stress from disrupting our immune systems.Read moreRead less