Molecular Cell Biology Of HNP22: Role In Alcohol Dependence
Funder
National Health and Medical Research Council
Funding Amount
$346,320.00
Summary
We used a differential screening procedure to detect changes in gene expression in the human alcoholic brain and described a novel gene, which we named hNP22, with increased expression in the superior frontal cortex of the alcoholic cases. This is the first report of a novel alcohol-responsive gene isolated from the human brain. We now propose to further explore the hNP22 gene, its product and its regulation in human brain tissue, and in a variety of experimental systems. We will determine how p ....We used a differential screening procedure to detect changes in gene expression in the human alcoholic brain and described a novel gene, which we named hNP22, with increased expression in the superior frontal cortex of the alcoholic cases. This is the first report of a novel alcohol-responsive gene isolated from the human brain. We now propose to further explore the hNP22 gene, its product and its regulation in human brain tissue, and in a variety of experimental systems. We will determine how protein expression correlates with the level of alcohol consumption. We will use animal and cell culture models to determine the response of the gene to various stimuli. We will express the recombinant protein to determine its function. It is likely that the gene product may be a component in an important signal pathway within neuronal cells and thus may represent a novel target for therapeutic intervention.Read moreRead less
Gene-environment Interactions And Experience-dependent Plasticity In The Healthy And Diseased Cerebral Cortex
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
Huntington's disease (HD) is a devastating illness in which movement disorders (including chorea) and mental problems progress for 10-20 years after onset, and inevitably lead to death. HD is caused by an expansion in a repeating segment of DNA in a single gene and is inherited by 50% of the offspring of sufferers. Despite this strong genetic factor, we have recent evidence from a mouse model, in which the human HD gene mutation has been inserted into the mouse genome, supporting a role for envi ....Huntington's disease (HD) is a devastating illness in which movement disorders (including chorea) and mental problems progress for 10-20 years after onset, and inevitably lead to death. HD is caused by an expansion in a repeating segment of DNA in a single gene and is inherited by 50% of the offspring of sufferers. Despite this strong genetic factor, we have recent evidence from a mouse model, in which the human HD gene mutation has been inserted into the mouse genome, supporting a role for environmental factors in disease onset and progression. Following on from our work showing that environmental enrichment delays disease and progression in this mouse model of HD, we are using experimental manipulations of the environment to examine effects on brain degeneration and behaviour. This project aims to investigate gene-environment interactions in HD, focusing on dysfunction of neurons in the cerebral cortex. The combination of behavioural, physiological, anatomical and molecular analysis of HD mice will bring us closer to a comprehensive understanding of HD. This will have implications for the development of new therapies for HD. Our environmental enrichment paradigm may also lead to development of occupational therapy strategies for HD and other neurological disorders. There are at least ten other fatal brain disorders which are caused by the same DNA repeat expansion in other genes. New insights into HD will therefore have implications for the understanding and development of therapeutics for these other DNA repeat expansion brain diseases. Furthermore, another devastating brain disorder which, like HD, involves abnormal protein interactions and dysfunction of the cortex, is Alzheimer's disease. Understanding HD may therefore also have implications for our understanding of Alzheimer's disease. Additionally, analysing control mice in this project will provide new information on mechanisms of plasticity in the normal cortex, which may underlie learning and memory.Read moreRead less
Development Of A Diagnostic Test For Bipolar Disorder (BD)
Funder
National Health and Medical Research Council
Funding Amount
$140,330.00
Summary
A unique test that monitors the rate of switching between the hemispheres of the brain in response to visual stimuli has been devised. A patent application covers an apparatus and test to measure the switching rate between the hemispheres and the way in which such measurements can be used as a means to diagnose bipolar disorder (BD). BD, also called manic depression, is a form of depression that currently affects over six million people worldwide with about three million in the USA alone. The co ....A unique test that monitors the rate of switching between the hemispheres of the brain in response to visual stimuli has been devised. A patent application covers an apparatus and test to measure the switching rate between the hemispheres and the way in which such measurements can be used as a means to diagnose bipolar disorder (BD). BD, also called manic depression, is a form of depression that currently affects over six million people worldwide with about three million in the USA alone. The condition has phases of mania and depression and periods of remittance. Full cycles of BD can occur as many as three times a year and for many patients, this is a lifelong condition. BD is effectively treated, once it is diagnosed. It is estimated that 20% of sufferers go undiagnosed and many more are misdiagnosed. The cost of mis- or non-diagnosis is measured by suicides, the financial burden on society with health care, loss of productivity etc, effects on family and associates, crime, etc. Diagnosis to date is achieved mainly by subjective means such as questionnaires. These instruments do not conclusively separate BD from other forms of depression and schizophrenia, for which treatment is quite different. Nor do they allow for factors such as substance abuse and other medical conditions that the patient may be suffering. BD is hereditary with the slow hemispheric switch rate being an indicator of the genetic trait. This phenomenon allows for an objective test for BD, even if an individual has not had an episode of BD. The slow switch allows relatively easy separation of a BD patient from those exhibiting symptoms that may have other causes.Read moreRead less
Intraocular Transplantation And Regeneration Of Retinofugal Pathways In Rodents
Funder
National Health and Medical Research Council
Funding Amount
$370,937.00
Summary
In the adult human brain and spinal cord there is little or no intrinsic capacity for replacement of lost or dying neurons, and there is minimal spontaneous repair of nerve fibre pathways. Thus traumatic injuries, stroke, or loss of neurons due to chronic degenerative disease result in functional impairments that are usually severe and long-lasting. The personal, social and economic costs associated with these neurological problems are enormous. New ways must be found of protecting and-or replen ....In the adult human brain and spinal cord there is little or no intrinsic capacity for replacement of lost or dying neurons, and there is minimal spontaneous repair of nerve fibre pathways. Thus traumatic injuries, stroke, or loss of neurons due to chronic degenerative disease result in functional impairments that are usually severe and long-lasting. The personal, social and economic costs associated with these neurological problems are enormous. New ways must be found of protecting and-or replenishing nerve cells in damaged CNS gray matter, and new methods are also required to help reconstruct fibre tracts after injury. Using the visual system as an experimental model, the aims of the proposed work are to develop novel transplantation and surgical strategies to: (i) Incorporate new cells into retinae that have been selectively depleted of endogenous neurons (ii) Promote the effective regeneration of large numbers of adult retinal axons through prosthetic peripheral nerve bridging grafts and into host CNS distal to the injury. The results obtained from the first series of studies will not only be of direct relevance to the future treatment of human retinal degenerative disorders, but will also increase our overall understanding of how best to ensure the differentiation and stable integration of different types of transplanted cells within the compromised host CNS. The second series of experiments should lead to an entirely new approach to nerve pathway reconstruction, relevant to both brain and spinal cord injuries. The ultimate aim of this experimental work is to improve the management and treatment of human CNS injury and disease, leading to better functional recovery and rehabilitation.Read moreRead less
Comparative Analysis Of Novel Transgenic Mouse Models For Brain And Islet Amyloidoses
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
We aim to understand what two highly prevalent diseases, the brain disorder Alzheimer's disease (AD) and the metabolic disorder Type 2 Diabetes mellitus (DM), have in common. Through understanding pathogenesis and the development of novel transgenic models our long-term research goal is to identify new drug targets, to develop screening assays and to patent new findings. Collectively, this hopefully leads to AD and DM drugs and reduces the socio-economic burden of both debilitating diseases.
Saccadic Eye Movements And The Neural Basis Of Visual Perception
Funder
National Health and Medical Research Council
Funding Amount
$570,828.00
Summary
The eye has a restricted central area that has good vision. We must make very frequent eye movements to build up a high resolution picture of a particular image. The term active vision is used to describe the requirement of coordinating the eye movements with the visual system. The study of active vision at the neural level requires experiments that combine single cell recording with behaviour. This study will explore which parts of the brain are involved in active vision in monkeys.
GENETIC FACTORS AND REGIONAL BRAIN ATROPHY IN THE DIAGNOSIS OF DEMENTIA WITH LEWY BODIES
Funder
National Health and Medical Research Council
Funding Amount
$605,151.00
Summary
The number of people with dementia is increasing in Australia as people live longer. Dementia sometimes has a genetic basis and identification of such cases has improved our understanding of the events leading to the destruction of the brain tissue. In the vast majority of people, the degenerative changes were previously thought to be as a result of Alzheimer's disease. However, our recent research, funded by the NHMRC, confirms international findings showing more than 25% of people with dementi ....The number of people with dementia is increasing in Australia as people live longer. Dementia sometimes has a genetic basis and identification of such cases has improved our understanding of the events leading to the destruction of the brain tissue. In the vast majority of people, the degenerative changes were previously thought to be as a result of Alzheimer's disease. However, our recent research, funded by the NHMRC, confirms international findings showing more than 25% of people with dementia have a different disease called Dementia with Lewy bodies or DLB. Of course identifying these patients occurs at death when the cells in the brain can be examined for Lewy bodies. We now know that the brain degeneration differs significantly in patients with this disease. However, it is still not possible to identify DLB in life with any certainty. This project aims to develop objective methods to clinically differentiate dementia patients. We will seek out families in which genetic influences may underly the disease and determine whether these factors differ from those found in other dementing illnesses. Also, our preliminary studies have observed volume loss in a particular brain region in pathologically confirmed DLB patients. We wish to do further measurements to determine if tissue loss in this region can clinically differentiate DLB patients. In addition, we will determine the reasons for the tissue loss by careful pathological studies.Read moreRead less