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.
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.
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.
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
Signalling Mechanisms Regulating Neurogenesis And Neurite Outgrowth
Funder
National Health and Medical Research Council
Funding Amount
$486,000.00
Summary
Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's, Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, there is a substantial body of evidence that has emer ....Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's, Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, there is a substantial body of evidence that has emerged in recent years, that has led to the view that repair of the central nervous system following injury of disease may indeed be a possibility. Effective neural repair is likely to require a multi-factorial approach, including blockage of neuronal death, replacement of lost neurons by neural stem cells, and regulation of appropriate subsequent neurite outgrowth and formation of correct connections. We have shown that a regulator of cytokine signaling, SOCS2, promotes neuronal differentiation and neurite outgrowth. This project aims to continue our investigations of the role of SOCS2 and interacting factors in regulating neuronal differentiation as well as substantially expanding our investigations into the role of SOCS2 in regulating neurite outgrowth, using both in vitro and in vivo models. An understanding of the mechanisms involved in these processes may allow us to derive therapies for the repair of the nervous system after injury or disease.Read moreRead less