NPY Suppresses Seizures And Modulates Thalamocortical Activity In Animal Models Of Generalized Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$386,020.00
Summary
Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled ....Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled with current medications. Recently there has been considerable interest in the role that chemical in the brain, such as neuropeptide Y (NPY), may play in epilepsy. The research proposed will examine the role of NPY in several animal models of absence epilepsy. We have recently shown that NPY suppresses absence seizures in a rat genetic model of generalised epilepsy, and that this appears to be mediated by Y2 receptors. This work will build on these novel findings, and determine the localisation of the effect within the brain, and the underlying mechanism. We will check NPY effects across several models in different species, a genetic rat model with spontaneous seizures, and in mice treated with a chemical to induce seizures. This will determine its broad applicability. We will also determine the effects of removal of NPY or NPY receptors on the effects of NPY on seizure expression. Finally, brain recording techniques will be applied to determine the mechanism and site within the brain underlying the protective actions of NPY. The project has the potential to provide novel insights into the role of NPY in the expression and modulation of absence seizures. NPY related mechanisms might represent targets for the development of a new class of therapeutic agents for the treatment of absence epilepsy. Targets that are identified as being important in the expression of absence seizures may also prove to be relevant in other types of generalised epilepsy syndromes.Read moreRead less
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
Using Mathematical Models To Assess The Impact Of Interventions To Reduce Sexually Transmitted Infections In Australia
Funder
National Health and Medical Research Council
Funding Amount
$562,276.00
Summary
Sexually transmitted infections (STIs) are an increasing public health problem in Australia. Australia's recent National Transmissible Infections Strategy identified chlamydia control, STI prevention in gay men and STIs in Aboriginal and Torres Strait Islander communities as priority areas. We propose to develop mathematical models of STI transmission and use these to help understand and identify the most cost-effective interventions to reduce the impact of STIs on Australian populations.
Centre For Translational Neuroscience: A Modular Platform For Translating Discovery Into Health Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$2,623,735.00
Summary
Clinical Centre of Research Excellence in Translational Neuroscience will provide people, pathways and resources to create a novel platform to take the outputs of Neuroscience Discovery programs though to improved patient outcomes for common brain diseases. A critical role will be to train and equip the best and brightest of the next generation of researchers to undertake internationally competitive translational neuroscience research that makes a difference to the health of our community.
THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
Targeting NPY Mechanisms In Rodent Models Of Generalised Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$437,637.00
Summary
This project will provide important information regarding the pharmacological mechanisms by which NPY acts to suppress seizures in animal models of epilepsy. It will provide strategies regarding potential new treatments of absence epilepsy.
The Final Common Channel: Measurement Of Nerve Excitability In Epilepsy.
Funder
National Health and Medical Research Council
Funding Amount
$301,376.00
Summary
Epilepsy may be due to either one single genetic mutation or a combination of several gene-environment interactions, affecting how ion channels function. It is not possible to directly interrogate channels in the living human brain but, because similar channels are found in peripheral nerve, much may be learned about aberrant channel function from peripheral nerve. This project aims to measure peripheral nerve excitability in epilepsy patients, using it as a marker of the final common pathway of ....Epilepsy may be due to either one single genetic mutation or a combination of several gene-environment interactions, affecting how ion channels function. It is not possible to directly interrogate channels in the living human brain but, because similar channels are found in peripheral nerve, much may be learned about aberrant channel function from peripheral nerve. This project aims to measure peripheral nerve excitability in epilepsy patients, using it as a marker of the final common pathway of channel dysfunction.Read moreRead less
Evaluating The Genetic Contribution To Rheumatic Heart Disease Pathogenesis In Australian Aboriginal And Torres Strait Islander Communities
Funder
National Health and Medical Research Council
Funding Amount
$1,782,074.00
Summary
Rheumatic heart disease is highly prevalent in Aboriginal people in Australia and leads to early cardiac disease. Despite decades of research, the underlying genetic mechanisms for why it occurs are not well understood. We are conducting a genetic study to better understand why some people are susceptible to RHD and others are not. The study will involve substantial Aboriginal leadership and consultation and will be a model for the conduct of genetic studies in Aboriginal populations.
The Effect Of Stress And Hypercortisolaemia On Limbic Epileptogenesis & Affective Disorder.
Funder
National Health and Medical Research Council
Funding Amount
$380,714.00
Summary
This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is ....This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is a bi-directional relationship, with the psychiatric conditions and stress also acting to aggravate the seizures and even predispose to the development of the epilepsy itself. Apart from gaining insights into causes of TLE, anxiety and depression, this framework has potential public health relevance suggesting approaches to the eventual primary and secondary prevention of both MTLE and its associated psychiatric co-morbidities, a neglected area at present. The use of an animal model allows investigation of aetiological processes that extend over the lifetime, which is exceptionally difficult to achieve in humans. Retrospective studies, such as case-control studies, although an indispensable research methods, are subject to bias and imprecision when it comes to measuring remote past exposures to stress, abuse, and deprivation. If the results of these experiments are consistent with our hypotheses, a very strong case would exist for exploring this relationship in human studies. The data would also provide a strong rationale for more aggressive detection and treatment of these psychiatric co-morbidities in TLE patients, in order to potentially modify the progression of the disorder as well as improve the quality of life of sufferers. The results of intervention studies in animal models may suggest specific mode of treatment to achieve this.Read moreRead less
Creating Sustainable Healthcare: Ensuring New Diagnostics Avoid Harms, Improve Outcomes, And Direct Resources Wisely
Funder
National Health and Medical Research Council
Funding Amount
$2,497,658.00
Summary
Novel imaging, biomarkers and genomic tests for risk assessment and early detection are emerging as major forces for change in clinical practice. While providing advances and new benefits for patients, new technologies can also have harmful, unintended consequences - overdiagnosis and overtreatment. This multidisciplinary CRE will investigate how to respond to emerging technologies to optimise health outcomes while avoiding harms and directing healthcare resources wisely.