Lipid Rafts, Amyloid Neurotoxicity And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$318,267.00
Summary
Alzheimer's disease is the major cause of dementia in the elderly. Individuals with Alzheimer's disease exhibit a slow decline in cognition which usually results in prolonged institutionalisation. This creates an enormous burden on society. The project aims to identify mechanisms which cause Alzheimer's disease. Specifically, it will examine how a component of the brain, known as the amyloid protein, contributes to nerve cell degeneration. It is hoped that by identifying these mechanisms, new ta ....Alzheimer's disease is the major cause of dementia in the elderly. Individuals with Alzheimer's disease exhibit a slow decline in cognition which usually results in prolonged institutionalisation. This creates an enormous burden on society. The project aims to identify mechanisms which cause Alzheimer's disease. Specifically, it will examine how a component of the brain, known as the amyloid protein, contributes to nerve cell degeneration. It is hoped that by identifying these mechanisms, new targets for drug development will be found.Read moreRead less
Molecular Determinants Of Inhibitory Synaptic Function Studied Using Mutant And Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Communication between nerve cells is the key to effective brain function and when disturbed, pathological states such as epilepsy, schizophrenia, fear and anxiety, spasticity and motor disorders ensue. This project is based on new data which suggests that the site of this communication, called the synapse, is a much more dynamic structure than previously thought. Based on our work to date, where we have demonstrated the recruitment of selected classes of neurotransmitter receptors into synapses, ....Communication between nerve cells is the key to effective brain function and when disturbed, pathological states such as epilepsy, schizophrenia, fear and anxiety, spasticity and motor disorders ensue. This project is based on new data which suggests that the site of this communication, called the synapse, is a much more dynamic structure than previously thought. Based on our work to date, where we have demonstrated the recruitment of selected classes of neurotransmitter receptors into synapses, our aim is to use a range of naturally occuring mice mutants, as well as transgenic mice to modulate the receptor levels and so to examine the role of synaptic function and synaptic dynamics. The outcomes of this project will provide fundamental new knnowledge aimed at understanding how communication in the nervous system works and may suggest ways in which modulation of this information flow could be used to treat disorders of brain function.Read moreRead less
Control Of Mastication By Periodontal Mechanoreceptors In Man
Funder
National Health and Medical Research Council
Funding Amount
$169,990.00
Summary
Despite the importance in chewing and speech, very little is known regarding the fine control of jaw muscles. A thorough understanding of the control of the jaw muscles is at the base of improved diagnosis and treatment of many chewing disorders. For example: We still do not understand the causes of the jaw muscle-joint pain disorder (temporomandibular dysfunction) which accounts for about 5 % of total dental patients. The current treatments, including pain killers, night plates and massage cure ....Despite the importance in chewing and speech, very little is known regarding the fine control of jaw muscles. A thorough understanding of the control of the jaw muscles is at the base of improved diagnosis and treatment of many chewing disorders. For example: We still do not understand the causes of the jaw muscle-joint pain disorder (temporomandibular dysfunction) which accounts for about 5 % of total dental patients. The current treatments, including pain killers, night plates and massage cure only about half of all patients. Improved diagnosis and treatment techniques require more precise elaboration of the neural and muscular mechanisms of chewing. Why do the chewing forces in toothless individuals, despite well fitting dentures, fall to about 20 % of the value in teethed individuals? Do jaw muscles in these subjects weaken because they get less feedback from the receptors around the teeth? How does the chewing force automatically adjust to overcome sudden or gradual changes in the characteristics of foodstuff? Although bite to bite changes in the chewing force is observed in subjects with natural teeth, no such changes occur in toothless subjects or subjects chewing with implanted bridges. How do the receptors adjust the activation of jaw muscles so that bite force is applied in the right direction and right amount at each bite? The aim of this study is to define the importance of the periodontal mechanoreceptors (tiny nerve cells that are situated between the roots of the teeth and the jaw bone that signal bite force to the brain) in the control of jaw muscles. This study will, therefore, illustrate the importance of keeping the teeth and gums healthy for the development of strong, smooth and well-controlled chewing forces, and potentially create opportunities to improve chewing (and thereby quality of life) in toothless individuals or those experiencing other difficulties in chewing.Read moreRead less
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
Synaptic Integration And Plasticity In The Rat Piriform Cortex
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project i ....The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project is to begin by studying one of the simplest regions of the cerebral cortex, the olfactory (or piriform) cortex. The olfactory cortex is an evolutionarily ancient region of cortex, with a simpler architecture than other cortical regions. Its task is to process the sense of smell, a primitive sense that is more elaborated in lower animals than in humans. The broad goal of our research is to understand, by studying the olfactory cortex of rats, how olfactory processing occurs at the level of nerve cells (neurons). We will use a number of powerful techniques - including microelectrode recording and laser microscopy - to measure the electrical properties of individual neurons. We will also study the synaptic connections between neurons, and how these connections change following memory-inducing stimuli. It is hoped that this work will shed light on how the healthy cortex is able to process and store information, and how brain diseases cause these functions to deteriorate.Read moreRead less
Neurexin And Neuroligin: A Code For Synaptic Development
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
As soon as we are born, we interpret our world through our senses, learn new information and lay down memory. These processes require molecules that connect neurons together. Mutations in genes encoding these molecules result in incorrect wiring of the brain and lead to mental disorders such as autism and schizophrenia. Using simple insect models, our project aims to unravel the fundamental mechanisms of how these molecules function in the brain and how their interaction controls behaviour.
IDENTIFICATION AND FUNCTION OF RECEPTORS ON SYMPATHETIC TERMINAL SCHWANN CELLS
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
The terminals of sympathetic nerves control many of the internal organs. Pharmacological intervention to promote or antagonize the effects of these terminals is very important in a number of different disease states of the autonomic nervous system. The present research proposal sets out to determine the way in which glial cells that partly envelop these terminals control their capacity to function.
Sulfonadyn-based Dynamin I-specific Inhibitors And Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$835,291.00
Summary
Epilepsy affects 1% of people, yet 30% do not respond to anti-epileptic drugs (AEDs). Traditional drug discovery fails to improve this situation. Our team discovered dynamin as a new target for better AED design and our lead sulphonadyns reduces seizures in animals. We will design better sulfonadyns that can ultimately be used for clinical trials by designing the drugs away from its actions outside of neurons. If successful, this will accelerate new AED development with less side-effects.
The Effect Of CPAP On Erectile And Endothelial Dysfunction In Impotent Men With Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$609,559.00
Summary
Erectile dysfunction is common in men with obstructive sleep apnea, due to vascular damage, which leads to heart attack. CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will establish if CPAP can also improve erectile and vascular endothelial dysfunction. These results will shed light on the mechanisms that underpin the relationship between OSA and Erectile Dysfunction.
The Contributions Of Different Sources Of Calcium To The Induction Of Long Term Potentiation
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
When we make memories, we alter the strength of synaptic connections between nerve cells.These changes are particularly marked in the hippopcampus ; a region of the brain involved in the formation of memories. The strength of a synaptic connection is altered if it activates a neurone sufficiently to cause a rise in the level of calcium ions. Calcium can be derived from several sources within the neurone. This project aims to assess the relative importance of these different sources of calcium in ....When we make memories, we alter the strength of synaptic connections between nerve cells.These changes are particularly marked in the hippopcampus ; a region of the brain involved in the formation of memories. The strength of a synaptic connection is altered if it activates a neurone sufficiently to cause a rise in the level of calcium ions. Calcium can be derived from several sources within the neurone. This project aims to assess the relative importance of these different sources of calcium in inducing increases in synaptic strength.Read moreRead less