Experience-dependent Maturation And Plasticity Of The Cerebral Cortex Mediating Schizophrenia-like Endophenotypes
Funder
National Health and Medical Research Council
Funding Amount
$384,199.00
Summary
We will use genetic mouse models of schizophrenia to understand how specific abnormal behaviours are caused, focusing on cells and molecules within the brain. We will investigate how the gene mutations disrupts communication between, and production of, brain cells (neurons), and the role of mental and physical activity. The results of this project will not only have implications for understanding schizophrenia, but also for other brain disorders involving cognitive problems, such as dementia.
Regulation Of Regeneration Of Dopaminergic Neurones In The Substantia Nigra
Funder
National Health and Medical Research Council
Funding Amount
$115,880.00
Summary
Parkinson's Disease (PD) results from the progressive loss of brain cells in the part of the brain called substantia nigra. These brain cells contain a chemical called Dopamine (DA). The symptoms of Parkinson's disease arise when about 80% these DA neurones are lost suggesting that some form of compensation must occur up to this point. In previous studies we have demonstrated that one mechanism for this compensation is through sprouting or branching of the remaining neurones. We have preliminary ....Parkinson's Disease (PD) results from the progressive loss of brain cells in the part of the brain called substantia nigra. These brain cells contain a chemical called Dopamine (DA). The symptoms of Parkinson's disease arise when about 80% these DA neurones are lost suggesting that some form of compensation must occur up to this point. In previous studies we have demonstrated that one mechanism for this compensation is through sprouting or branching of the remaining neurones. We have preliminary evidence about the way this is sprouting and regeneration is controlled. The aim of this grant is to explore in detail the mechanisms whereby sprouting is induced and regulated. The significance of this study is that it may provide insights into the way in which regulation of regeneration of the nervous system is controlled. It has specific applications to therapies for Parkinson's disease.Read moreRead less
Parkinson's Disease is caused by injury to a group of brain cells called the Basal Ganglia. Our current ideas about how this part of the brain works is dominated by a well know theory. This theory requires that the output pathway of the basal ganglia to have a negative or inhibitory influence on its target. However there are numerous reasons why this would be unlikely, including some recent evidence from experiments in our laboratory. The purpose of this study is to undertake an extensive re exa ....Parkinson's Disease is caused by injury to a group of brain cells called the Basal Ganglia. Our current ideas about how this part of the brain works is dominated by a well know theory. This theory requires that the output pathway of the basal ganglia to have a negative or inhibitory influence on its target. However there are numerous reasons why this would be unlikely, including some recent evidence from experiments in our laboratory. The purpose of this study is to undertake an extensive re examination of the output paths of the Basal Ganglia. If our suspicions are correct, it will lead to a review of the whole way in which we think the Basal Ganglia works.Read moreRead less
The Role Of Rnd Genes During Cortical Neurogenesis And Cell Migration
Funder
National Health and Medical Research Council
Funding Amount
$410,384.00
Summary
In order for the brain to function properly, tens of billions of neurons within it first have to be born, then find their proper location before connecting with other neurons in a highly ordered fashion. Failure of these key processes heavily impacts on subsequent brain function, and have been shown to underlie several disorders including epilepsy. This study will investigate how members of the Rnd gene family control cell production and positioning within the developing brain.
Relationship Between Nigral Injury, Dopamine Handling And Dyskinesia In Parkinsonism
Funder
National Health and Medical Research Council
Funding Amount
$65,685.00
Summary
Parkinson's Disease is a disabling condition that results from loss of nerve cells (neurones) in the part of the brain known as the substantia nigra (SN). These neurones make dopamine. Symptoms become apparent when 80% of these neurones are gone, suggesting that compensation can occur in the brain. Dopamine can be replaced with the drug L-dopa. Unfortunately this benefit is not sustained and is frequently marred by the production of unpleasant writhing wriggling movements called dyskinesia. Thes ....Parkinson's Disease is a disabling condition that results from loss of nerve cells (neurones) in the part of the brain known as the substantia nigra (SN). These neurones make dopamine. Symptoms become apparent when 80% of these neurones are gone, suggesting that compensation can occur in the brain. Dopamine can be replaced with the drug L-dopa. Unfortunately this benefit is not sustained and is frequently marred by the production of unpleasant writhing wriggling movements called dyskinesia. These movements can also complicate the treatment for schizophrenia and other neurological conditions. The way the brain compensates for loss of SN neurones and why dyskinesia occur is unknown. However we present a hypothesis that the mechanisms for compensation also produce the dyskinesia. We have shown that an injury to the SN results in a compensatory response of vigorous sprouting of the surviving dopamine neurones. This sprouting may also explain why dyskinesias occur. The aim of this study is to establish whether the degree of compensatory response corresponds with the severity of dyskinesia and how this compensatory response can be modified or regulated.Read moreRead less
Molecular Mechanisms Mediating Experience-dependent Cellular Plasticity And Cognitive Deficits In Huntingtons Disease
Funder
National Health and Medical Research Council
Funding Amount
$550,387.00
Summary
We will use a genetic mouse model of Huntington's disease (HD), to understand how cognitive disorders (dementia) are caused, focusing on cells and molecules within the brain. We will investigate how the HD gene mutation disrupts communication between brain cells (neurons), as well as disrupting production of new cells (via adult neural stem cells). The results of this project will not only have implications for treating HD but also for other diseases involving dementia, such as Alzheimer's.
Parkinson s disease (PD) is a progressively disabling movement disorder afflicting over 25,000 Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemcials and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration. Current symptomatic treatments give sufferers some relief for a period of time by boosting the amount of these depleted chemicals in the brain. Howe ....Parkinson s disease (PD) is a progressively disabling movement disorder afflicting over 25,000 Australians. It is caused by the degeneration of specific nerve cells in the brain that produce certain chemcials and patients suffer from an inability to move fluently (or ultimately at all). At present we do not know what triggers this neurodegeneration. Current symptomatic treatments give sufferers some relief for a period of time by boosting the amount of these depleted chemicals in the brain. However, the underlying cellular degeneration continues unabated until such treatments are no longer effective. It is necessary to determine the reason for the cell loss in the brain in order to develop successful long-term treatments for this disabling disorder. There have been a number of animal models for PD developed. Comparing the type of tissue damage associated with the cell loss in these models shows that signs of brain inflammation occur prior to the loss of nerve cells. This feature consistently occurs regardless of the method used to produce the disease model. However, inflammation has been poorly studied in PD. Part of the present proposal is to analyse the brain tissue from patients with PD in order to document whether inflammation is also a consistent feature in the regions affected by the disease. Other central nervous system disorders in which inflammation is thought to play a pivotal role often have some genetic predisposition to the disorder and there is evidence of an immune response in their blood. We also wish to examine these aspects in patients with PD. Overall, our study will provide the necessary evidence for or against a primary role for inflammation in the disease process causing the ongoing degeneration in PD. If significant indications for a primary role for inflammation are found, treatments specifically targeting inflammation (already available) can be trialled to slow or stop the neurodegeneration.Read moreRead less