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
Investigation Of The Function Of The Scaffolding Protein LIN-2/CASK In Cholinergic Synapses
Funder
National Health and Medical Research Council
Funding Amount
$911,656.00
Summary
Scaffolding proteins play vital role in synapses to maintain the function of the nervous system. One important scaffolds LIN-2/CASK has been implicated in autism disorders and has profound effect on synaptic function. Here we investigate the function of LIN-2/CASK and its binding partners in cholinergic synapses to dissect how they regulate synaptic transmission.
In pilot studies, we have found that specific genes are modulated by long-term alcohol intake in a discrete part of the brain that drives habitual behaviours. We will now repeat these studies in post-mortem brain tissue from human alcoholics and age-matched controls. In addition, we will further characterise the functional consequences of long-term alcohol intake within this specific brain region and test new approaches to reduce the urge to consume alcohol.
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
Muscarinic Receptors In The Human Brain: In Health And In Sickness
Funder
National Health and Medical Research Council
Funding Amount
$394,408.00
Summary
Schizophrenia is a severe mental illness, with sub-optimal treatment outcomes. New drugs are being designed to provide more effective treatment. To understand the effects of these drugs, we need to know which brain cells have the protein these new drugs target and which cells are affected in schizophrenia. Our project will determine the localisation of this drug target; this knowledge will help the development of better treatments for schizophrenia.
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.