Dynamic Trafficking Of Amino Acid Transporters At Synapses And Their Role In Regulating Neurotransmission
Funder
National Health and Medical Research Council
Funding Amount
$421,219.00
Summary
Brain cells release chemical neurotransmitters to activate their neighbours. The most abundant neurotransmitter is glutamate, which mediates most of the communication in the brain. Following release, this neurotransmitter must be rapidly recycled to prevent levels being depleted and neurotransmission failing. The subject of this grant is to understand what molecules and pathways are used to recycle glutamate in the brain, and how its supply is controlled to sustain continual brain activation.
Interactions Between Developmental NMDA Receptor Dysfunction, Genetic Vulnerability And Early-life Stress In Schizophrenia: Studies Of Dysbindin Mutant Mice And Living Individuals At High Risk Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$347,457.00
Summary
This project will investigate two key pathways implicated in schizophrenia: glutamatergic (excitatory) neurotransmission and stress signalling. We will study how glutamatergic deficits emerge across postnatal development, in the presence or absence of early-life stress, in a schizophrenia-relevant mouse model, and investigate the interactions between stress and glutamatergic deficits in neuroepithelial cells from living individuals at high risk of schizophrenia.
Regulation Of Glutamate Receptor Trafficking By The Calcium- And Lipid-binding Protein, Copine-6
Funder
National Health and Medical Research Council
Funding Amount
$548,690.00
Summary
Abnormal levels of cell surface receptors in neurons can lead to a variety of debilitating neurological disorders and neurodegenerative diseases. These levels are tightly regulated through the orchestrated movements of receptors from inside the neuron to the cell surface. In this project we will examine how the transport of cell surface receptors is regulated by an intracellular signalling molecule, called copine, which is important in both epilepsy and Alzheimer’s disease.
Experience-dependent Cellular Plasticity And Cognitive Deficits In Mouse Models Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$444,318.00
Summary
Schizophrenia is a brain disorder involving psychiatric symptoms which include abnormalities of cognitive processes. We are using mouse models to understand the cause of cognitive deficits, at the level of molecules and cells. One discovery we have made is that the generation of new neurons, from adult neural stem cells, are abnormal in a specific brain region of these mice. This research will provide new information regarding the cause of cognitive deficits, and will have implications for the d ....Schizophrenia is a brain disorder involving psychiatric symptoms which include abnormalities of cognitive processes. We are using mouse models to understand the cause of cognitive deficits, at the level of molecules and cells. One discovery we have made is that the generation of new neurons, from adult neural stem cells, are abnormal in a specific brain region of these mice. This research will provide new information regarding the cause of cognitive deficits, and will have implications for the development of new treatments.Read moreRead less
The PDZ Scaffold NHERF-1; A Novel Regulator Of Astrocyte Function?
Funder
National Health and Medical Research Council
Funding Amount
$444,500.00
Summary
Astrocytes are a vital cell type in the human brain. They provide nutrients to neurons, remove toxic chemicals such as glutamate (a neurotransmitter), as well as stabilising the levels of molecules such as water and ions such as sodium, bicarbonate and potassium. Astrocytes perform all these tasks by means of specialised protein molecules called transporters that are embedded in their cell membranes. These transporters are not uniformly distributed; they are positioned in those parts of the astr ....Astrocytes are a vital cell type in the human brain. They provide nutrients to neurons, remove toxic chemicals such as glutamate (a neurotransmitter), as well as stabilising the levels of molecules such as water and ions such as sodium, bicarbonate and potassium. Astrocytes perform all these tasks by means of specialised protein molecules called transporters that are embedded in their cell membranes. These transporters are not uniformly distributed; they are positioned in those parts of the astrocyte membranes where the particular biological job has to be performed. How are they targeted to, and retained in these places? We have preliminary data suggesting that a specialised protein called NHERF-1, can bind a group of these proteins, called glutamate transporters, thereby anchoring them to the skeleton of the cell. If we are correct then we should be able to manipulate this interaction, both in live brain tissues, and in simple cell culture systems, using a variety of physiological and molecular biology techniques. If we are correct in our hypothesis, then our findings will have immense value in trying to reduce damage that occurs in human brains in conditions such as strokes, where a breakdown in the control of glutamate around neurons causes extensive and irreversible brain damage.Read moreRead less
Glutamate is one of the major neurotransmitters in the brain. It plays a very important role in most brain functions such as the ability to learn and the development of memory, but the lack of control of glutamate concentrations in the brain also underlies many pathological changes that cause neurological disorders such Alzheimer's disease, disability following a stroke, motor neurone disease and Parkinson's disease. These diseases place an enormous social and economic burden on society and in o ....Glutamate is one of the major neurotransmitters in the brain. It plays a very important role in most brain functions such as the ability to learn and the development of memory, but the lack of control of glutamate concentrations in the brain also underlies many pathological changes that cause neurological disorders such Alzheimer's disease, disability following a stroke, motor neurone disease and Parkinson's disease. These diseases place an enormous social and economic burden on society and in order to better understand and treat these diseases it is important to understand some of the fundamental biochemical processes that underlie both normal and pathogical functions of the key neurotransmitter glutamate. This project will investigate how the concentrations of glutamate are tightly regulated to maintain normal brain function and also to avoid the potentially pathological consequences when these control mechanisms fail.Read moreRead less