Which Neurons Maintain Sympathetic Vasomotor Tone?
Funder
National Health and Medical Research Council
Funding Amount
$567,918.00
Summary
High blood pressure is a major risk factor for cardiovascular disease, a major burden of disease worldwide. High levels of nerve activity that cause the blood vessels to constrict elevating blood pressure are characteristic of hypertension. We do not know which brain cells set and maintain this nerve activity. We will identify these cells, determine how they function and what regulates them. Ultimately we could control these cells treating the cause of hypertension or when clinical need arises.
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.
The brain regulates body temperature by a series of mechanisms, including the control of how much blood flows to the skin to lose or retain heat. The project aims to locate the brain temperature receptors and brain pathways that do this, using an animal model, the rat. At present they are not known.
Brain Pathways For Neurally-mediated Fever: From Vagal Afferent To Sympathetic Output To Brown Adipose Tissue Via Brain
Funder
National Health and Medical Research Council
Funding Amount
$405,223.00
Summary
Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins ....Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins (cytokines) are released. The cytokines enter the blood stream and are transported to the brain. Recently, the existence of another signalling pathway has been demonstrated. The pathway is via a special peripheral sensory nerve, the abdominal vagal sensory nerve. However, special neural pathways in the brain have not yet been clarified, even though several neural relay stations have been proposed. To elucidate neural pathways transmitting information of infection to the brain, both input and output of the pathway need to be specified. Specific outputs other than body temperature have not been determined, so far. I have recently developed a new reflex model, in which I focus on sympathetic nerves supplying the specialised fat tissue as an output as well as the vagus sensory nerve as an input. The fat tissue, brown adipose tissue (BAT), generates heat. When the vagus sensory nerve is stimulated electrically, BAT sympathetic nerve is activated. We were very exited when we discovered the potency of the combination in our rat model. We are now ready to elucidate brain pathways for neurally-mediated fever, using our new reflex model. Signalling to the brain via the nervous system is faster than via the blood stream, and thus must be very important for the earliest phase of fever. Understanding the neural pathways by which the brain perceives peripheral infection and triggers fever may promote beneficial aspects of the acute-phase immune reaction.Read moreRead less
Investigation Of Neuregulin Precessing By Beta-site APP Cleaving Enzyme And Gamma Secretase In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$46,715.00
Summary
Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more s ....Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more selective therapies with less side-effects.Read moreRead less
Developing Novel Selective Glycine Receptor Potentiators As A Means To Control Pain.
Funder
National Health and Medical Research Council
Funding Amount
$552,647.00
Summary
It has been estimated that >3M Australians suffer from pain at a cost to the economy of >$34B, with chronic pain (persisting beyond 1-6 mths) accounting for ~half this burden. There is an urgent and compelling social and economic case for the development of safer and more effective pain therapeutics. This project takes inspiration from a new class of Australian marine natural products that selectively regulate a key pain pathway, and will optimize and develop these as a new class of pain d ....It has been estimated that >3M Australians suffer from pain at a cost to the economy of >$34B, with chronic pain (persisting beyond 1-6 mths) accounting for ~half this burden. There is an urgent and compelling social and economic case for the development of safer and more effective pain therapeutics. This project takes inspiration from a new class of Australian marine natural products that selectively regulate a key pain pathway, and will optimize and develop these as a new class of pain drug.Read moreRead less