Hypothalamic Orexin Neurons And The Medullary Sympathoadrenal Centre: A Key Role In Glucose Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$577,957.00
Summary
Hypoglycaemia or low blood sugar is a major side-effect of the treatment of diabetes. Exposure to hypoglycaemia results in changes in the brain (neuroplasticity) that reduce the awareness of hypoglycaemia, often with serious consequences. Hypoglycaemia triggers the production of several hormones including adrenaline which restore normal blood glucose. This process is incompletely understood. This research project will identify key components of the neurocircuitry that controls blood sugar.
A Randomised Double Blinded Placebo Controlled Trial Of Adrenaline In Cardiac Arrest.
Funder
National Health and Medical Research Council
Funding Amount
$200,500.00
Summary
It is estimated that in excess of 30,000 Australians per year suffer a cardiac arrest, mostly occurring outside of hospital. This sudden and often unpredictable event commonly occurs as a result of acute heart disease, injury, drug overdose and many other illnesses which affect both males and females of all ages. Unfortunately, the survival of those suffering a cardiac arrest remains poor. Best evidence to date suggests overall survival from cardiac arrest to be in the order of about 5%. While t ....It is estimated that in excess of 30,000 Australians per year suffer a cardiac arrest, mostly occurring outside of hospital. This sudden and often unpredictable event commonly occurs as a result of acute heart disease, injury, drug overdose and many other illnesses which affect both males and females of all ages. Unfortunately, the survival of those suffering a cardiac arrest remains poor. Best evidence to date suggests overall survival from cardiac arrest to be in the order of about 5%. While the survival for those suffering cardiac arrest remains poor, the rapid initiation of cardiopulmonary resuscitation (CPR) and defibrillation has been clearly shown to improve outcome. While defibrillation and CPR have been shown to be beneficial, the use of vasoactive drugs such adrenaline has not been proven to improve survival in cardiac arrest. This is despite adrenaline being internationally recommended as first line drug therapy in the advanced life support (ALS) management of cardiac arrest. It is now well acknowledged that clinical trials need to be undertaken to determine the clinical effects of adrenaline when used for cardiac arrest. The purpose of this study is to randomise patients suffering a cardiac arrest to receive either adrenaline (according to standard ALS guidelines) or a placebo. All other care for both groups will be the same and in accordance with current ALS guidelines. In this way we will be able to determine the effects of adrenaline on outcome, particularly survival, following cardiac arrest. The study will run for three years and involve all cardiac arrests attended by the Ambulance Service in Perth.Read moreRead less
Deciphering The Molecular Steps Leading To The Potentiation Of Neuronal Exocytosis By Arachidonic Acid
Funder
National Health and Medical Research Council
Funding Amount
$273,000.00
Summary
Release of hormones and neurotransmitters relies on a process called exocytosis which involves SNARE proteins: syntaxin1A and SNAP-25 on the target plasma membrane and VAMP on the vesicular membrane. Availability of the t-SNARE on the plasma membrane is believed to play a major role in controlling the amount of exocytosis. Syntaxin1A bound to Munc18 constitute an 'unproductive-reserve' pool of closed Syntaxin that cannot interact with SNAP-25. Intracellular messengers capable of releasing Syntax ....Release of hormones and neurotransmitters relies on a process called exocytosis which involves SNARE proteins: syntaxin1A and SNAP-25 on the target plasma membrane and VAMP on the vesicular membrane. Availability of the t-SNARE on the plasma membrane is believed to play a major role in controlling the amount of exocytosis. Syntaxin1A bound to Munc18 constitute an 'unproductive-reserve' pool of closed Syntaxin that cannot interact with SNAP-25. Intracellular messengers capable of releasing Syntaxin1A from Munc18 thereby making it available to interact with SNAP-25, are foreseen to play a major role in potentiating exocytosis - a process with ramification for memory and learning. We have identified arachidonic acid, a lipidic messenger which fullfil this role. For the first time we are in a position to manipulate at the molecular level different pools of SNARE proteins with direct implications for our understanding of the mechanism of secretion. Very few models are currently available to understand how learning and memory occur in the brain. Our research points to a new direction: the amount of 'active' and 'unproductive-reserve' pools of SNARE proteins present on the plasma membrane of neurosecretory cells are in dynamic equilibrium and arachidonic acid, a second messenger capable of trans-synaptic action, can modify this equilibrium resulting in an increase of the amount of 'active' SNARE thereby potentiating the amount of transmitter-hormone released by exocytosis. Importantly, this research lays the basis for a dynamic view of the secretory mechanism with important implications for treatment of diseases such as diabetes and neurodegenerative diseases. Our hope is that by understanding at the molecular level how secretory cells regulate the amount of their secretion, we will be in a position to modify these parameters in order to counteract illnesses of the nervous system.Read moreRead less