Unravelling A New Fatty Acid Pathway Involved In Neuroexocytosis And Memory
Funder
National Health and Medical Research Council
Funding Amount
$539,631.00
Summary
This proposal build on the establishment by our laboratory of the assay capable of detecting free fatty acids, with great accuracy and sensitivity. Using this assay we have uncovered a completely new pathway highlighting the production of saturated free fatty acids linked to learning and memory. We will fully define how this pathway is regulated in the brain.
Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Long-term memory systems and the human brain. Impairment of memory is a ubiquitous feature of human brain disease. A better understanding of memory processing in the brain is key to the development of better tests for the detection and monitoring of disease progression as well as the application of improved methods of rehabilitation for patients with acquired brain injury. This project will provide the catalyst for the development of a National Memory Disorders Research Centre that would be the ....Long-term memory systems and the human brain. Impairment of memory is a ubiquitous feature of human brain disease. A better understanding of memory processing in the brain is key to the development of better tests for the detection and monitoring of disease progression as well as the application of improved methods of rehabilitation for patients with acquired brain injury. This project will provide the catalyst for the development of a National Memory Disorders Research Centre that would be the focus for multidisciplinary cognitive neuroscience research. The ultimate aim would be the translation of basic neuroscience into effective tools that will impact the health outcome of the ageing population.Read moreRead less
The role of the prefrontal cortex in responding to a changing world. This proposal will test a novel theory of frontal brain function that emphasises the contrasting role of two regions of the prefrontal cortex in dealing with the changing nature of the world. It will provide novel insights in the the psychology and neural underpinnings of the control of behaviour. This will add to our basic knowledge of brain function, feeding into our understanding of human mental disorders such as schizophren ....The role of the prefrontal cortex in responding to a changing world. This proposal will test a novel theory of frontal brain function that emphasises the contrasting role of two regions of the prefrontal cortex in dealing with the changing nature of the world. It will provide novel insights in the the psychology and neural underpinnings of the control of behaviour. This will add to our basic knowledge of brain function, feeding into our understanding of human mental disorders such as schizophrenia and dementia. It will also provide training in psychology and behavioural neuroscience for Honours and Doctoral students.Read moreRead less
Human long-term memory and social cognition: an integrated cognitive neuroscience approach. Impairment of memory is a ubiquitous feature of the dementias and a better understanding of memory processing in the brain is key to the development of better tests for the early detection and monitoring of disease progression. The study of social cognition is relevant to a range of developmental, psychiatric and neurological disorders. This project will provide the catalyst for the development of a Natio ....Human long-term memory and social cognition: an integrated cognitive neuroscience approach. Impairment of memory is a ubiquitous feature of the dementias and a better understanding of memory processing in the brain is key to the development of better tests for the early detection and monitoring of disease progression. The study of social cognition is relevant to a range of developmental, psychiatric and neurological disorders. This project will provide the catalyst for the development of a National Memory and Cognitive Disorders Centre that would be the focus for multidisciplinary cognitive neuroscience research. The ultimate aim would be the translation of basic neuroscience into effective tools that will impact the health outcomes of the ageing population.Read moreRead less
Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Austra ....Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Australian patients, use novel techniques to identify biomarkers for IFNb response, evaluate the diagnostic and therapeutic value of the biomarkers, and develop a new test for NABs. Tailored use of this drug, and possible new therapeutic targets, will result, benefiting the patient and community.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560916
Funder
Australian Research Council
Funding Amount
$323,400.00
Summary
Magnetic resonance in humans: Equipment for neuroscience studies. The structure, function and biochemistry of the human brain can now be assessed non-invasively using magnetic resonance (MR) techniques. A 3 Tesla MR facility with half its time available for research has recently been established at POWMRI. This application seeks state-of-the-art equipment so that the facility can optimise its research potential and enhance its scientific output. Research is directed to understanding how the nor ....Magnetic resonance in humans: Equipment for neuroscience studies. The structure, function and biochemistry of the human brain can now be assessed non-invasively using magnetic resonance (MR) techniques. A 3 Tesla MR facility with half its time available for research has recently been established at POWMRI. This application seeks state-of-the-art equipment so that the facility can optimise its research potential and enhance its scientific output. Research is directed to understanding how the normal brain functions, how deficits in function develop, and how the function and structure of the brain change with age. This grant will help establish an internationally-competitive, broadly-based facility which is dedicated to understanding the human brain.Read moreRead less
Investigating the role of Zona Incerta RXFP3+ cells in learning and memory. Learning and memory are fundamental to human and animal behaviour. We identified a specific population of cells in the zona incerta of the brain, where activation inhibits expression of memory, and facilitates the acquisition of new learning. Aside from our observations, nothing is currently known about the anatomy and function of these cells. This project aims to map how they connect to the rest of the brain, to observe ....Investigating the role of Zona Incerta RXFP3+ cells in learning and memory. Learning and memory are fundamental to human and animal behaviour. We identified a specific population of cells in the zona incerta of the brain, where activation inhibits expression of memory, and facilitates the acquisition of new learning. Aside from our observations, nothing is currently known about the anatomy and function of these cells. This project aims to map how they connect to the rest of the brain, to observe how these connections are recruited during learning and memory, and then to test their function experimentally. The outcomes will extend the known neural circuitry that controls learning by defining how and where these unexplored pathways fit within it; thus advancing knowledge regarding neural regulation of behaviour.
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Central nervous system cytokines and morphine analgesia. Morphine remains the drug of choice for the management of moderate-to-severe pain, however its clinical effectiveness is compromised by the fact that morphine's analgesic (pain reducing) efficacy becomes less effective the more it is administered.. This project will examine how analgesic tolerance develops from a completely new approach: Namely, how stimulation of the immune system within the central nervous system is a crucial factor in t ....Central nervous system cytokines and morphine analgesia. Morphine remains the drug of choice for the management of moderate-to-severe pain, however its clinical effectiveness is compromised by the fact that morphine's analgesic (pain reducing) efficacy becomes less effective the more it is administered.. This project will examine how analgesic tolerance develops from a completely new approach: Namely, how stimulation of the immune system within the central nervous system is a crucial factor in the development of tolerance. Modulation of analgesia by the immune system has not been systematically studied and provides a potentially fertile ground for the development of new techniques in the management of clinical pain.Read moreRead less