The Brain As A Therapeutic Target For Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$923,432.00
Summary
In heart failure there is a large increase in sympathetic nerve activity to the heart that leads to damage to the heart and sudden death. We have shown that lesion of the area postrema, a brain nucleus that senses hormones in the blood, reduces nerve activity to the heart and, importantly, improves cardiac function. We aim to translate these findings into a treatment that can be used clinically, which our findings compellingly indicate should improve cardiac function in heart failure
Targeting The Sympathetic Nervous System To Reduce The Burden Of Fatty Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$728,152.00
Summary
The metabolic syndrome is characterised by abdominal obesity, high blood pressure and an increased risk of diabetes development. It is clear from our own observations that the sympathetic nervous system (SNS) is important in the generation of obesity-related illness and, through its stimulation of the liver, plays an important role in the development of obesity-related liver disease. We will target the SNS in order to reduce the burden of obesity-related liver disease.
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
Use of an animal model to understand mechanisms underlying reductions in body weight associated with use of the laparoscopic adjustable gastric band. At least one in ten Australians is classified as morbidly obese and as such are eligible for bariatric surgery. Those undergoing the surgery will achieve an average excess weight loss of up to 60 per cent, they will have reduced or eliminated diabetes and will appreciably improve their prospects of survival. These experiments aimed at understandin ....Use of an animal model to understand mechanisms underlying reductions in body weight associated with use of the laparoscopic adjustable gastric band. At least one in ten Australians is classified as morbidly obese and as such are eligible for bariatric surgery. Those undergoing the surgery will achieve an average excess weight loss of up to 60 per cent, they will have reduced or eliminated diabetes and will appreciably improve their prospects of survival. These experiments aimed at understanding the mechanisms underpinning this success have the potential to further improve surgical approaches and outcomes and provide insights that will better enable weight loss therapies for all overweight and obese Australians.Read moreRead less
Organisation of the cerebral cortex- what, if anything, is a cortical area? Currently, much effort is being directed towards elucidating the roles of different regions of the cerebral cortex. "Maps" of cortical areas have become essential points of reference, exerting a powerful influence on the way we think about the brain. However, is it really appropriate to model the cortex as a mosaic of well-defined areas? This project will challenge the assumptions underlying current brain mapping efforts ....Organisation of the cerebral cortex- what, if anything, is a cortical area? Currently, much effort is being directed towards elucidating the roles of different regions of the cerebral cortex. "Maps" of cortical areas have become essential points of reference, exerting a powerful influence on the way we think about the brain. However, is it really appropriate to model the cortex as a mosaic of well-defined areas? This project will challenge the assumptions underlying current brain mapping efforts. Its main benefits will be the refinement of strategies for brain mapping, including potential for better
application/interpretation of available medical technology, and unique insights on the mechanisms of development and evolution of the nervous system.
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Understanding brain mechanisms that control autonomic function. This project aims to understand the how the brain regulates sympathetic nerve activity, thereby increasing our understanding of the biology and function of nascent neurons on the adult brain stem. This challenges the current notion that new neurons are only made during development. The project will also determine how brain inflammation impacts blood-brain barrier function and affects sympathetic nerve regulation. The basic fundament ....Understanding brain mechanisms that control autonomic function. This project aims to understand the how the brain regulates sympathetic nerve activity, thereby increasing our understanding of the biology and function of nascent neurons on the adult brain stem. This challenges the current notion that new neurons are only made during development. The project will also determine how brain inflammation impacts blood-brain barrier function and affects sympathetic nerve regulation. The basic fundamental insights and conceptual advances into how autonomic function is controlled by the brain will provide a better understanding of these fundamental processes and will contribute to Australia’s priority research areas to improve health and advance product development.Read moreRead less
The cortical location of hunger and thirst: a multifunctional study in sheep. The escalating problems associated with obesity are immense. These effects contribute to a global epidemic that now eclipses both infectious diseases and (ironically) undernutrition in its proportions. The effects of disorders of thirst are less apparent but potentially devastating albeit on a smaller scale. The elderly and psychotic in the community have impaired thirst mechanisms which impacts on their life in a dra ....The cortical location of hunger and thirst: a multifunctional study in sheep. The escalating problems associated with obesity are immense. These effects contribute to a global epidemic that now eclipses both infectious diseases and (ironically) undernutrition in its proportions. The effects of disorders of thirst are less apparent but potentially devastating albeit on a smaller scale. The elderly and psychotic in the community have impaired thirst mechanisms which impacts on their life in a dramatic way particularly during prolonged hot weather. The aims of these experiments are to understand the basic brain mechanisms that underpin these drives. This understanding will have far reaching repercussions for the community both in terms of promoting good health and in preventative health care.
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Understanding how the brain uses sensory information to guide reaching and grasping movements. Reaching, grasping and manipulating objects are crucial aspects of our daily lives, which are performed so effortlessly that they tend to be taken for granted. We know however that these functions take a relatively long time to mature (think of a baby learning how to get an object), and that they can be impaired by brain lesions involving a region called the posterior parietal cortex. We also know that ....Understanding how the brain uses sensory information to guide reaching and grasping movements. Reaching, grasping and manipulating objects are crucial aspects of our daily lives, which are performed so effortlessly that they tend to be taken for granted. We know however that these functions take a relatively long time to mature (think of a baby learning how to get an object), and that they can be impaired by brain lesions involving a region called the posterior parietal cortex. We also know that this region has multiple subdivisions, but how exactly these interact in allowing the sensory information to guide arm and hand muscles is unknown. Discovering how this happens in terms of cellular interaction can have profound implications for the creation of new technologies such as artificial limbs and autonomous robots, and result in health benefits.Read moreRead less
The processing of sensory information within cortical circuits. This project aims to improve our knowledge of neuronal activity during sensory perception and therefore shed light on overall brain function during behaviour. Understanding how dendrites receive and process this information is crucial to understanding brain function during sensory processing and perception. This proposal aims to characterise dendritic activity during sensory input and discover how this activity contributes to behavi ....The processing of sensory information within cortical circuits. This project aims to improve our knowledge of neuronal activity during sensory perception and therefore shed light on overall brain function during behaviour. Understanding how dendrites receive and process this information is crucial to understanding brain function during sensory processing and perception. This proposal aims to characterise dendritic activity during sensory input and discover how this activity contributes to behavioural tasks. In particular, the project plans to investigate activity of different dendritic domains during sensory perception and sensory-based behaviour. The project seeks to improve our knowledge of the importance of dendrites in transforming information from the sensory environment and highlight the cellular and network mechanisms contributing to behaviour.Read moreRead less