A Study Of Muscarinic Receptors In Brain Tissue Obtained Postmortem From Subjects With Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$354,810.00
Summary
The research outlined in this proposal will examine the molecular make up of certain regions of the human brain and determine if components within those regions are altered in tissue from subjects with schizophrenia. Schizophrenia is a serious psychiatric illness that affects approximately 1% of the Australian population and the research described in this proposal seeks to help understand the cause of the illness and-or to assist in the development of new drugs with which to treat the illness. T ....The research outlined in this proposal will examine the molecular make up of certain regions of the human brain and determine if components within those regions are altered in tissue from subjects with schizophrenia. Schizophrenia is a serious psychiatric illness that affects approximately 1% of the Australian population and the research described in this proposal seeks to help understand the cause of the illness and-or to assist in the development of new drugs with which to treat the illness. The goal of the research outlined in this proposal is to determine if there are changes in specific molecules in the brain, termed muscarinic receptors. The muscarinic receptors are one way that a chemical in the brain called acetylcholine can communicate with the nerve cells in the brain. Acetylcholine is known to control important functions of the brain such as in memory, cognition and learning, all of these functions are thought to be affected in schizophrenia. Importantly, the control of all these functions involve muscarinic receptors and therefore, changes in those receptors could well produce some of the symptoms of schizophrenia. We now wish to extend our early studies which suggest there may be changes in muscarinic receptors in the brain of subjects with schizophrenia to determine which of the 5 muscarinic receptors are affected in which region of the brain by the pathology of the illness. From our existing data, we would predict that these studies will add weight to the argument that muscarinic receptors are altered in schizophrenia and provide vital information as to how drugs that target these receptors may be used to treat the illness.Read moreRead less
THE ROLE OF CHANGES IN THE HIPPOCAMPAL SEROTONIN TRANSPORTER IN THE PATHOLOGY OF SCHIZOPHRENIA
Funder
National Health and Medical Research Council
Funding Amount
$340,317.00
Summary
Schizophrenia is a serious mental illness that affects approximately 1% of the Australian population. The cause of the illness remains unknown but many lines of evidence suggest that changes in the function of a chemical neurotransmitter, serotonin, are involved in the disease process. We have shown a change in the serotonin transporter, a critical component of the brain which controls the actions of serotonin, in the an area of the brain called the hippocampus in subjects with schizophrenia. Th ....Schizophrenia is a serious mental illness that affects approximately 1% of the Australian population. The cause of the illness remains unknown but many lines of evidence suggest that changes in the function of a chemical neurotransmitter, serotonin, are involved in the disease process. We have shown a change in the serotonin transporter, a critical component of the brain which controls the actions of serotonin, in the an area of the brain called the hippocampus in subjects with schizophrenia. This proposal seeks to elucidate the mechanisms by which a change in the serotonin transporter may affect other important molecules in the hippocampus. In addition, we will continue our research designed to assess the usefulness of the 5,7-dihydroxytryptamine treated rat as a possible tool for the study of changes in the serotonin transporter.Read moreRead less
A Novel Knockin Model To Test The Role Of Nicotine Acting On Alpha4 Acetylcholine Receptors In Complex Behaviours
Funder
National Health and Medical Research Council
Funding Amount
$581,315.00
Summary
Cigarette smoking is the single largest preventable cause of death and disease in Australia and worldwide. Nicotine contained in tobacco products acts on brain nicotine receptors, which plays an intrinsic role in addiction. One type of receptor for nicotine found in regions of the brain associated with drug-seeking behaviour is called alpha4 nicotinic receptors. We have made a mouse with a mutation in this nicotine receptor to study nicotine addiction and anxiety.
Protein Partners Of Rapsyn That Regulate Acetylcholine Receptor Clustering
Funder
National Health and Medical Research Council
Funding Amount
$411,000.00
Summary
Spinal nerves control our limb muscles by releasing chemical signals directly onto the surface of muscle fibres that they contact. These chemical signalling contacts are called synapses. They are like the synapses between nerve cells in our brains but easier to study, meaning that we can make more rapid progress in understanding how synapses work. The sensor receptors for chemical signals at the nerve-to-muscle synapse are held in place on the muscle fibre surface by a protein called rapsyn. In ....Spinal nerves control our limb muscles by releasing chemical signals directly onto the surface of muscle fibres that they contact. These chemical signalling contacts are called synapses. They are like the synapses between nerve cells in our brains but easier to study, meaning that we can make more rapid progress in understanding how synapses work. The sensor receptors for chemical signals at the nerve-to-muscle synapse are held in place on the muscle fibre surface by a protein called rapsyn. In turn, rapsyn must be organized by other chemical signals from the nerve, but we don't know exactly how this happens. When the receptors become disorganized at the synapse, in diseases such as Myasthenia Gravis, we lose control of our muscles. This project will employ newly developing techniques of proteomics and genomics to identify new proteins that bind to rapsyn and to test how they work to organize receptors at the synapse. By identifying the proteins that control rapsyn we may be able to develop new treatments for Myasthenia Gravis that restore the function of the synapse with less side effects than current therapies.Read moreRead less
Sacral Parasympathetic Innervation Of Distal Bowel
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
Not a topic for polite conversation, normal movements of the colon and rectum are essential for good health and a sense of wellbeing. Constipation, diarrhoea, incontinence and pain result from disordered motility. One major control mechanism is the parasympathetic innervation. While we know of its importance, how it works in health and diseases is poorly understood. This project will use state-of-the-art techniques to study this pathway in order to understand its role in health and disease