Molecular Pathogenesis Of Amino Acid Neurotransmission In Human Chronic Alcoholism
Funder
National Health and Medical Research Council
Funding Amount
$378,750.00
Summary
Brain damage resulting from long-term alcohol abuse is localized to discrete regions of the brain, and may selectively affect certain specific functions of nerve cells. It appears that alcoholism affects processes which control the excitability in discrete regions of the brain, and hence can cause them to be over-stimulated. It is known that if brain cells are excessively stimulated for long periods, they are in danger of being killed. This study will determine how the tissue s capacity to proce ....Brain damage resulting from long-term alcohol abuse is localized to discrete regions of the brain, and may selectively affect certain specific functions of nerve cells. It appears that alcoholism affects processes which control the excitability in discrete regions of the brain, and hence can cause them to be over-stimulated. It is known that if brain cells are excessively stimulated for long periods, they are in danger of being killed. This study will determine how the tissue s capacity to process glutamate, the brain s major natural excitant, is altered in the regions which are selectively damaged in alcoholics. How these processes are affected by heredity, and by diseases commonly associated with alcoholism such as cirrhosis of the liver, will also be explored. An understanding of how selective brain damage occurs in alcoholics will help us to devise new drug therapies to combat and prevent it. As well, selective brain damage is found in a great many neurological diseases, so this study will provide a model which may help to dene general processes which give rise to localised neurological damageRead moreRead less
Development Of The Commissural Plate And Its Role In Forebrain Commissure Development
Funder
National Health and Medical Research Council
Funding Amount
$529,565.00
Summary
During development, neurons in one hemisphere of the brain connect and communicate with neurons in the opposite hemisphere. Such neural connections between the two hemispheres are called commissures, which are large bundles of axons (neural-wires) that cross the midline of the brain. There are three commissures in the forebrain: the corpus callosum, the hippocampal commissure and the anterior commissure. This wiring of the brain is essential to its proper function. When these connections don't f ....During development, neurons in one hemisphere of the brain connect and communicate with neurons in the opposite hemisphere. Such neural connections between the two hemispheres are called commissures, which are large bundles of axons (neural-wires) that cross the midline of the brain. There are three commissures in the forebrain: the corpus callosum, the hippocampal commissure and the anterior commissure. This wiring of the brain is essential to its proper function. When these connections don't form, the brain cannot integrate and process information in fundamental ways. Over 50 different human congenital disorders are associated with the malformation of one or more of these forebrain commissures. This proposal investigates the hypothesis that a midline structure, called the commissural plate (CP), regulates the development of all forebrain commissures. The CP was first described anatomically at the turn of the 20th century in a number of different species, and in humans in 1968. However, since this time, no papers have been published on the CP. Experiments in this proposal will use modern neuroanatomical techniques, particularly magnetic resonance imaging, molecular and mouse mutagenesis techniques, and axon guidance assays, to study the CP. We will test the hypothesis that there is something fundamentally unique about the CP as the midline crossing point for all commissural axons. We generate mouse mutants that disrupt only dorsal CP formation and then determine whether the subsequent development of the dorsal commissures occurs. We also perform molecular expression, and imaging analyses on human foetal brains. Our goal is to provide an understanding of what developmental events are disrupted in human congential disorders resulting in midline brain malformations and agenesis of the forebrain commissures. Understanding the basis of these disorders will lead to more accurate diagnoses and potentially their prevention through genetic counseling.Read moreRead less
Genes Important For Early Brain Development Are Also Important For Adult Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
I committed to understanding of how the brain develops, grows and regenerates. My laboratory is active in finding a cure for brain injury following brain trauma or brain ischemia. I have discovered that the genes that drive neuron migration and wiring in the fetus also function in the adult brain to improve neuron survival and regeneration. Probing the function of these genes will deliver twin benefits in preventing brain disorder in the newborn and treating brain disease in the adult.