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.
Neurotransmitters mediate the communication between nerve cells in the brain. Once released at the synapse - the contact site between nerve cells - neurotransmitters propagate signals to neighbouring neurons. To allow fast and accurate signal processing in the brain neurotransmitters must be removed rapidly from the site of action. This resets the signal transduction process so that the next nerve impuls can be transmitted. Removal of neurotransmitters is accomplished by transporters, which capt ....Neurotransmitters mediate the communication between nerve cells in the brain. Once released at the synapse - the contact site between nerve cells - neurotransmitters propagate signals to neighbouring neurons. To allow fast and accurate signal processing in the brain neurotransmitters must be removed rapidly from the site of action. This resets the signal transduction process so that the next nerve impuls can be transmitted. Removal of neurotransmitters is accomplished by transporters, which capture the neurotransmitters and bring them back into neurons and astrocytes, the two major cell types in the brain. Malfunction of these transporters can cause mood disorders, Parkinsons's disease and may play a role in the onset of amyotrophic lateral sclerosis and other neurodegenerative disorders. In this project we try to identify novel neurotransmitters transporters, which are likely to play an important role in neurotransmission. Previously, these transporters were assigned as orphan transporters to indicate our lack of understanding. However, recent results from our laboratory now allows to identify the function of these transporters. Elucidation of the physiological role of these transporter will provide the basis to study their function and role in health and disease.Read moreRead less
Transfer Of Glutamine Between Astrocytes And Neurons
Funder
National Health and Medical Research Council
Funding Amount
$255,500.00
Summary
Brain tissue is comprised of only a few different cell types. These are classified as neurons, glial cells, and cells of mesodermal origin. Glial cells are the most abundant cell type in the brain and include cells known as astrocytes. There is increasing evidence that astrocytes are actively involved in the maintenance and regulation of neuronal function. This study focuses on the mechanisms by which astrocytes supply neurons with precursors for the formation of signalling molecules (neurotrans ....Brain tissue is comprised of only a few different cell types. These are classified as neurons, glial cells, and cells of mesodermal origin. Glial cells are the most abundant cell type in the brain and include cells known as astrocytes. There is increasing evidence that astrocytes are actively involved in the maintenance and regulation of neuronal function. This study focuses on the mechanisms by which astrocytes supply neurons with precursors for the formation of signalling molecules (neurotransmitters) released from neurons in the transmission of nerve impulses. It will establish how these processes are controlled and also try to develop inhibitors that interfere with this process . The project tries to elucidate whether astrocytes actively regulate neuronal functions by regulating precursor supply. The work will make a significant contribution to our understanding of how astrocytes regulate neuronal activity, a process that may be critical in conditions such as stroke and epilepsy. A better understanding of the physiology of astrocytes might lead to improved treatments for these disturbances of brain function.Read moreRead less
The Role Of The Glutamine Transporter SNAT3 In Ion Transport, Cell Signaling And Ammonia Detoxification
Funder
National Health and Medical Research Council
Funding Amount
$393,249.00
Summary
Hepatic encephalopathy is a syndrome observed in patients with liver cirrhosis and is caused by increased amounts of ammonia in the blood. The proposed project investigates a transporter that is involved in ammonia and glutamine metabolism in liver and brain. The two organs are critical to the pathology of liver failure and ammonia toxicity resulting from reduced liver function. The transporter thus could become a drug target for a variety of liver diseases.
Effect Of Oral Glutamine On GLP-1 And Insulin Secretion And Glycaemia In Humans.
Funder
National Health and Medical Research Council
Funding Amount
$397,444.00
Summary
Diabetes is an ever increasing problem with serious complications. We will investigate whether glutamine, one of the most common amino acids (protein building blocks) in the body, has a beneficial effect on blood glucose and insulin levels in the body in people who have type 2 (non-insulin dependent) diabetes. If so, glutamine supplementation may represent a novel, cheap and palatable way of improving outcomes and preventing the development of complications in people with type 2 diabetes.
Astrocyte Regulation Of Ammonia And Glutamate In Neonatal Hypoxia-Ischaemia
Funder
National Health and Medical Research Council
Funding Amount
$523,804.00
Summary
Lack of oxygen is a common problem for newborn infants, ocurring during events such as a difficult labour, and can lead to brain damage. We have discovered that a protein in the brain which normally removes ammonia (a toxic product of metabolism) is rapidly lost after a brief period of low oxygen. We propose that a build up of ammonia in the brain may be a key damaging event in hypoxia-related brain injury, and that it will be ameniable to therapeutic intervention.