What Contributes To Regional Vulnerability In Neurodegenerative Diseases? A Study Of Familial Cases.
Funder
National Health and Medical Research Council
Funding Amount
$456,655.00
Summary
Unfortunately, as many people live longer, more and more are afflicted by degenerative changes that affect their brain. These neurodegenerative diseases are usually relentlessly progressive and with time render patients incapable of many normal functions. For some families with certain genetic defects, these diseases occur aggressively and early. We would like to study the brains of patients from these families because in most cases the proteins affected by the gene defect have been identified. ....Unfortunately, as many people live longer, more and more are afflicted by degenerative changes that affect their brain. These neurodegenerative diseases are usually relentlessly progressive and with time render patients incapable of many normal functions. For some families with certain genetic defects, these diseases occur aggressively and early. We would like to study the brains of patients from these families because in most cases the proteins affected by the gene defect have been identified. However, despite knowing this important information, the reasons for the death of brain cells are still not understood. This project will provide important new information on which brain cells died in these patients and on the relationship between such cell death and any cellular protein changes. By comparing patients with different genetic defects we will be able to identify the main cellular mechanisms underlying these degenerative changes. This information is essential for the rational design of further experiments aimed at reducing the suffering of all patients with neurodegenerative diseases or at eliminating these diseases altogether.Read moreRead less
Neurotransmitter transporters are very good drug targets because modulation of their activity can lead to up and down regulation of neurotransmitter concentrations and thereby influence signalling pathways in the brain. This can be very useful in treating various neurological disorders and also altering normal brain functions such as learning and memory. In this project we will develop a detailed understanding of how glutamate transporters work and in so doing will be in a better position to des ....Neurotransmitter transporters are very good drug targets because modulation of their activity can lead to up and down regulation of neurotransmitter concentrations and thereby influence signalling pathways in the brain. This can be very useful in treating various neurological disorders and also altering normal brain functions such as learning and memory. In this project we will develop a detailed understanding of how glutamate transporters work and in so doing will be in a better position to design subtype and transporter-specific compounds. These compounds will be very useful in defining the role of glutamate transporter subtypes in normal and pathological states and may be useful in treating neurological disorders such as Alzheimer's disease, schizophrenia, ishaemia following a stroke, and motor neurone disease.Read moreRead less
Neurocognitive Studies Of Reward Sensitivity In Opiate Addiction And Its Influence On Addiction-related Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$258,275.00
Summary
Drug abuse is the greatest single preventable risk factor for physical illness and death in Australians . Our understanding of the neural and cognitive mechanisms that contribute to the transition from drug use to addiction is not yet complete. The current proposal investigates cognitive control dysfunction, most notably the impulsivity for reward seen in drug addiction that is known to predict the transition from drug use to addiction and relapse during treatment.
If Childhood Primary Snoring Resolves, Do Neurocognition And Behaviour Also Improve?
Funder
National Health and Medical Research Council
Funding Amount
$568,067.00
Summary
Sleep breathing disorders (SBD) are common and affect around 10% of all children. Previous research however has shown that sleep disorders are often not recognised or considered important enough to report to general practitioners. Thus, the true incidence of sleep disorders in Australian children is not known. Nevertheless, even the mildest SBD, primary snoring, has been associated with significant deficits in daytime learning, memory, intelligence, attention and problematic behaviour. In severe ....Sleep breathing disorders (SBD) are common and affect around 10% of all children. Previous research however has shown that sleep disorders are often not recognised or considered important enough to report to general practitioners. Thus, the true incidence of sleep disorders in Australian children is not known. Nevertheless, even the mildest SBD, primary snoring, has been associated with significant deficits in daytime learning, memory, intelligence, attention and problematic behaviour. In severe cases of childhood SBD (i.e. sleep apnoea syndrome), removal of the tonsils and adenoids has been shown to improve the learning and behaviour problems. Thus there is increasing pressure on doctors to treat primary snoring in children with surgery to improve their intellectual functioning. However, recent evidence in children has shown that snoring may resolve naturally in up to 50% of cases over one to two years. In addition to the risks of surgery, the large number of children who may have a natural resolution of snoring suggestst that the pressure to treat primary snoring in may not be justified. This study will be the first to determine the prevalence of childhood snoring and associated problems in the Australian community. We also aim to discover whether snoring and the associated intellectual deficits persist over time during childhood. We will identify frequent snorers and healthy non-snorers in children aged 5-10 years old, using parental questionnaires. We will then study 75 snorers and 75 non-snorers in more detail, monitoring them with overnight sleep studies and questionnaires 2 years apart, to see if snoring, intellectual function and behavioural problems persist over time. This information will improve the health of Australian children by determining the prevalence of childhood SBD and persistence of associated deficits such as in learning, memory and behaviour.Read moreRead less
This project will test the proposal that rising follicle-stimulating hormone (FSH) levels in ageing females directly accelerate reproductive failure and bone loss , major public health issues due to delayed childbearing and our rising ageing population. We have developed a unique mouse model with elevated FSH levels that cause premature female infertility. We will now use this model to determine the direct effects of high FSH upon ovarian and uterine function, as well as bone loss with age.
Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a grade ....Twin and family studies show schizophrenia has a genetic basis. Attempts to find and characterise the underlying genes have not been successful so far. A main reason for this is that insufficient attention has been paid to the complexity of the underlying genetic architecture of the disorder. The pathway from genes to symptoms of schizophrenia is likely to involve elementary processes at neuronal and neural circuitry levels that vary between individuals and this variation is reflected in a graded susceptibility to schizophrenia. During the last three years we have recruited a large number of families with at least one family member diagnosed with schizophrenia. The proband and all participating first-degree relatives have been assessed with a neurocognitive test battery including measures of sustained attention, working memory, speed of information processing, auditory verbal learning and executive function. Analysis of the neurocognitive data on this sample produced strong evidence that several measures are altered in patients with schizophrenia and a proportion of their asymptomatic first-degree relatives compared to unrelated normal controls. In the study we will systematically search the human genome for DNA markers linked to these measures. This will set the stage for the systematic search and characterisation of the underlying genes. This will allow us to better understand the predisposition to develop schizophrenia. In the individual case it is likely that this vulnerability results from a high-risk combination of a number of relatively common alleles which contribute to basic neural processes.Read moreRead less
Sleep Disordered Breathing And Neurocognitive Function In Children Post-adenotonsillectomy: Three Year Follow-up
Funder
National Health and Medical Research Council
Funding Amount
$266,536.00
Summary
Snoring is very common and affects at least 10% of children, or an estimated 0.25 million children in Australia. It is associated with deficits in a wide range of neurocognitive areas including intelligence, memory, reasoning, learning and behaviour. We have recently studied a group of 53 snoring children both before and six months after removal of their tonsils and adenoids, to treat suspected upper airway obstruction associated with their snoring. We found that prior to surgery, intelligence, ....Snoring is very common and affects at least 10% of children, or an estimated 0.25 million children in Australia. It is associated with deficits in a wide range of neurocognitive areas including intelligence, memory, reasoning, learning and behaviour. We have recently studied a group of 53 snoring children both before and six months after removal of their tonsils and adenoids, to treat suspected upper airway obstruction associated with their snoring. We found that prior to surgery, intelligence, memory, reasoning, language and behaviour were significantly reduced, by up to 10% compared to 53 non-snoring control children matched by age, gender, social class and area of residence. To our great surprise, at six months after surgery we found that although sleep and behaviour improves, intelligence, memory, reasoning and language development do not. We now wish to study these same children at 3 years after tonsils and adenoids removal, as we believe that if the deficits that we described at 6 months are still present, they are likely now to be permanent. Given the degree of deficit that we have found in snoring compared to non-snoring children, even 6 months after the snoring group of children have been treated, if still present at 3 years post-surgery then it is likely that these deficits will affect the children's future learning potential and academic success. In turn, this would suggest that early identification and treatment of sleep-related upper airway obstruction is critical in preventing long-term deficits in children's daytime functioning and behaviour.Read moreRead less
Body Mass Index And Mortality In Aboriginal Australians In Northern Territory: A Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$136,220.00
Summary
The ultimate goal of this study is to define a healthy weight range for Aboriginal people. To fulfil this goal, we will investigate the health implications of body weight and weight change in Aboriginal communities. We will assess the association between body weight (as measured by body mass index) and the risk of death by examining how the death rate changes with body weight. The findings will have important implications for health professionals to provide adequate advice to Aboriginal Australi ....The ultimate goal of this study is to define a healthy weight range for Aboriginal people. To fulfil this goal, we will investigate the health implications of body weight and weight change in Aboriginal communities. We will assess the association between body weight (as measured by body mass index) and the risk of death by examining how the death rate changes with body weight. The findings will have important implications for health professionals to provide adequate advice to Aboriginal Australians, and for Aboriginal people to adopt a healthy life style in relation to body weight. Due to the differences in body shape and physiological and environmental factors between Aborigines and other populations, the optimal body weight obtained from other populations may not be applicable to Aboriginal communities. Do males and females have different optimal body weights? Do old and young people have different optimal body weights? This study will provide evidence for answering various questions like these. Individuals with different characteristics may have different optimal body weight values. Such information is useful for the development and modification of dietary guidelines for Aboriginal Australians. The results on the health impact of weight change are important for guiding weight control programs in Aboriginal communities.Read moreRead less