Targeting Autism With Macrocephaly Using Mechanism Based Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$831,652.00
Summary
Autism affects a large number of children in our community and currently there is a lack of any medication to treat its core pathology. In this grant we will study the underlying biochemical changes in the brain that result in autism through the development of a new mouse model of the disorder. This mouse model will then be used test drugs to identify therapeutic targets for the treatment of autism.
The Role Of Reelin-signalling On Cortical Neuron Migration
Funder
National Health and Medical Research Council
Funding Amount
$716,196.00
Summary
Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of d ....Disorders that occur during brain development can lead to abnormal behaviours traits such as anxiety and altered social interactions, plus abnormalities in neuronal function and information processing. The region of the brain responsible for originating the motor, sensory and cognitive functions of a human is the cortex. This brain region is comprised of two major types of neurons that are arranged in a highly organized manner. One captivating aspect of the brain is that during early stages of development neurons are generated in one part of the brain and migrate great distances to a final destination. It is therefore necessary during development to have a well-orchestrated, controlled series of events that lead to the correct positioning and association of neurons. The precise functions of many gene products involved in this process are not known. One major advancement in the development of the cortex is the discovery of the protein Reelin which is found in the outermost region of the developing cortex. Mutations in Reelin, in humans, have been implicated in the causation of schizophrenia and mood disorders. These disease states are the result of altered migration of neurons in the cortex. The research proposed in this application is designed to understand the precise process of how two types of neurons migrate and assemble in the cortex. Technology today allows us to visualize, in culture, neurons as they migrate in real-time. This is referred to real time-lapse imaging and allows the researcher the ability to examine how external factors, affect migration of cortical neurons. We will determine how Reelin is involved in this process and our research will elucidate the fundamental process of cortical brain development.Read moreRead less
The amygdala is a part of the brain that processes and lays down emotional memories. Dysfunction in the amygdala is responsible for anxiety related disorders such post-traumatic stress disorder. I will study the neural circuits in the amygdala using innovative recordings and stimulation techniques. These studies will provide insight into the circuits that underpin anxiety related neurological disorders and provide targets for development of novel anxiolytic agents.
Neurogenesis In The Amygdala And Hippocampus: A Role In Learnt Fear?
Funder
National Health and Medical Research Council
Funding Amount
$780,396.00
Summary
It has long been thought that neurons are only born once and then slowly die. Learning and memory formation is thought to occur by changes in the strength of connections between living neurons. However, the hippocampus is now known to produce new neurons throughout life. We have found that neurons are also born in the adult amygdala. In this project we will study how neurogenesis affects learning and memory formation that involve the hippocampus and amygdala.
Glutathione is a natural antioxidant, which is known to protect cells in the body from chemical damage. A small part of the glutathione in cells is found in the mitochondria, a structure that is involved in producing the chemical energy needed for normal cell function. The mitochondria are also involved under some circumstances in promoting the death of cells. Although glutathione in general has been well studied, much less attention has been paid to the function of glutathione in mitochondria, ....Glutathione is a natural antioxidant, which is known to protect cells in the body from chemical damage. A small part of the glutathione in cells is found in the mitochondria, a structure that is involved in producing the chemical energy needed for normal cell function. The mitochondria are also involved under some circumstances in promoting the death of cells. Although glutathione in general has been well studied, much less attention has been paid to the function of glutathione in mitochondria, particularly in cells from the brain. Our recent studies indicate that this mitochondrial pool of glutathione is particularly important in limiting the death of cells from the brain when exposed to damaging substances that are increased in some diseases. Thus, the capacity of mitochondrial glutathione to deal with such substances might be a factor in determining the extent of cell loss in the brain, which is an important determinant of symptoms in some of the major neurological diseases. Consistent with this possibility, we have obtained evidence indicating that decreases in glutathione in the mitochondria contribute to the cell death and brain damage that results from a stroke. In our proposed studies, we will investigate the function of mitochondrial glutathione in the two major cell populations from the brain, neurons and astrocytes. We will characterise the protective role of the glutathione and investigate how it enters the mitochondria and what factors influence the amount that is present. This will provide new insights into the function of glutathione in the mitochondria and could also suggest novel approaches for manipulating this antioxidant pool. We will also study models of stroke and some related brain disorders to more directly test the role of this antioxidant in disease and to assess whether manipulating the content of glutathione in the mitochondria has the potential to reduce damage and improve function in these disordersRead moreRead less
Development of normal brain function requires information transfer and integration from outside and within the brain. Normal brain wiring is guided by genetic and environmental cues, whose relative contributions remain controversial. This project investigates the physiological and behavioural consequences of abnormal brain wiring, and the potential for controlled environments and targeted interventions to overcome the deficits. Relevance includes neurotrauma as well as mental illnesses.
Toward Cell-replacement Therapy For Parkinson's Disease: Investigating Endogenous Dopamine Neurogenesis In The Adult Mouse Substantia Nigra
Funder
National Health and Medical Research Council
Funding Amount
$577,957.00
Summary
Death of a particular type of cell in the brain causes the movement symptoms of Parkinson's disease (PD) (e.g. tremor). This study investigates how these cells are normally replaced, and whether stimulating their replacement can alleviate movement symptoms in an animal model of PD. Fulfillment of these aims will deliver vital information about how we might delay and better treat the movement symptoms of PD.
The Functional Role Of Slit-Robo Signaling In Interneuron Migration.
Funder
National Health and Medical Research Council
Funding Amount
$172,500.00
Summary
In the developing brain of vertebrates interneurons undergo directed migration to form complex networks that result in the regulation of neuronal processes. Failure or imbalance of these neuronal networks is known to cause pilepsy and mental retardation. The aim of this project is to investigate the guidance cues, specifically Slit-Robo signalling, that direct the migration of interneurons within the brain.
Glial Reactivity During The Post-acute Phase Of Stroke: A Target For Promoting Functional Recovery
Funder
National Health and Medical Research Council
Funding Amount
$547,307.00
Summary
Recent studies suggest that the development of a type of scar around damaged tissue in the brain following a stroke can limit recovery. Our studies will improve understanding of events leading to scar formation and will test whether modifying these events can improve functional recovery in experimental stroke. The studies have excellent potential to identify targets for treatments that will reduce the long-term debilitating effects of stroke even when administered well after its onset.
Parkinson's Disease (PD) is one of the most common neurodegenerative disorders. Its incidence increases steadily with age affecting approximately 1% of the population at age 65 and up to 5% by the age of 85. At the time of diagnosis, patients suffer from a range of motor impairments that worsen over time. Pathologically these patients are characterised by the accumulation of a protein known as alpha-synuclein in specific types of nerve cells in their brain. However, the function of this protein ....Parkinson's Disease (PD) is one of the most common neurodegenerative disorders. Its incidence increases steadily with age affecting approximately 1% of the population at age 65 and up to 5% by the age of 85. At the time of diagnosis, patients suffer from a range of motor impairments that worsen over time. Pathologically these patients are characterised by the accumulation of a protein known as alpha-synuclein in specific types of nerve cells in their brain. However, the function of this protein is unknown. This proposal will clarify the role of alpha-synuclein in PD and normal CNS function and provide new potential therapeutic targets for the treatment of PD and other neurodegenerative disorders in which oxidative stress, excitotoxicity and central nervous system trauma have been implicated.Read moreRead less