The Role Of Neuronal Hyper-excitability In An Animal Model Of Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$558,170.00
Summary
Every day at least one person in Australia dies of the fatal and untreatable adult neurodegenerative disease of amyotrophic lateral sclerosis (motor neuron disease). This research examines the factors driving early increases in neural activity which may lead to the loss of upper and lower motor neurons in adulthood. The use of new methods to suppress production of specific proteins causing increased neural activity may lead to novel treatments for this disease.
The corticospinal pathway is the major route from the brain to the spinal cord for the control of voluntary movement in people. Little is known about how transmission through this pathway might alter with activity. It is known that, elsewhere in the brain, connections between nerve cells can be made stronger or weaker by specific patterns of activity and it is thought that such changes underlie learning and memory. We propose that similar changes might happen in the spinal cord at the connection ....The corticospinal pathway is the major route from the brain to the spinal cord for the control of voluntary movement in people. Little is known about how transmission through this pathway might alter with activity. It is known that, elsewhere in the brain, connections between nerve cells can be made stronger or weaker by specific patterns of activity and it is thought that such changes underlie learning and memory. We propose that similar changes might happen in the spinal cord at the connection between the nerve cells which carry signals from the brain and the nerve cells which carry the signals out to the muscle. This project will demonstrate that the connections in the pathway from the brain to the muscle can be strengthened or weakened in a controlled way by imposed patterns of activity. In addition, we know that after voluntary contractions, there are dramatic changes in the way signals in this pathway are transmitted to muscles. After brief strong voluntary contractions, muscle responses are immediately reduced. After longer contractions in which the muscles become fatigued, the reduction is followed by an increase in responses which can last many minutes. Thus, this project will also study changes in the pathway from the brain to the muscle after natural activity. The effects of changes induced by artificial or natural activity on the control of voluntary movement will also be investigated. Understanding how activity drives changes in the pathway that controls voluntary movement is important for all situations that involve learning motor tasks. These include normal development and learning of motor skills, as well as rehabilitation after all kinds of nerve or muscle injury. It is also important in understanding motor changes that occur when activity is altered by disorders like spinal cord injury or stroke. Improved understanding of the processes occuring should allow improvement in rehabilitation therapies.Read moreRead less
Novel Assessments Of The Central And Peripheral Control Of The Human Hand
Funder
National Health and Medical Research Council
Funding Amount
$365,105.00
Summary
This is a study of how the human hand works. The hand is supremely adapted for manual skills ranging from writing and playing a musical instrument to non-verbal communications via gesture and pointing. How is the range of hand skills achieved? We are motivated to study this because the ability of the hand to recovery from some neurological disorders, particularly stroke, is very poor. One important element in virtually all activities of the hand is precise movement of the thumb. The tip of the t ....This is a study of how the human hand works. The hand is supremely adapted for manual skills ranging from writing and playing a musical instrument to non-verbal communications via gesture and pointing. How is the range of hand skills achieved? We are motivated to study this because the ability of the hand to recovery from some neurological disorders, particularly stroke, is very poor. One important element in virtually all activities of the hand is precise movement of the thumb. The tip of the thumb is flexed by a single muscle, a muscle only present in humans. We want to determine how this muscle works, and how the force it produces affects the whole hand. We will use specialised neurophysiological techniques to do this in human volunteers. There is no comparable animal model for this type of work due to significant differences at both the level of the brain and the level of the muscle. Second, we want to understand better how the cells in the spinal cord which control the hand (and other) muscles work. We have two new ways to do this, including a novel technique which can activate these cells with a form of stimulation that may help us improve functional electrical stimulation. Finally, with 27 bones and more than 25 muscles which operate it, the hand is not simple to control. We will use a new apparatus to measure how well it is controlled, and we will directly stimulate the motor areas of the brain to evaluate the control. From this, we will come up with new understanding, as well as new stimulus and measurement techniques that can be applied to patients with impaired hand function, as occurs all too often after stroke.Read moreRead less
RNAi Therapeutic Intervention Of Human Viral Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$584,117.00
Summary
Human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. HMPV is emerging as a major cause of morbidity and life-threatening respiratory tract disease in infants, young children and the elderly worldwide. No treatment is currently available. The objectives of this proposal are to develop novel antiviral drugs that silence the expression of viral genes and to examine protection against the disease.
The Role Of Secretory Antibodies In Mucosal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
This proposal will address the role of the antibodies that are present in all secretions from the gut, the lungs, the eye and mouth in maintaining the health of the mucosal (ie mucous covered) tissues from which they originate. It has long been presumed that these antibodies stop bacteria and other pathogens adhering to the surface of mucosal tissues. Our preliminary findings suggest that they have another very important role in removing excess inflammatory material from beneath the lining of th ....This proposal will address the role of the antibodies that are present in all secretions from the gut, the lungs, the eye and mouth in maintaining the health of the mucosal (ie mucous covered) tissues from which they originate. It has long been presumed that these antibodies stop bacteria and other pathogens adhering to the surface of mucosal tissues. Our preliminary findings suggest that they have another very important role in removing excess inflammatory material from beneath the lining of the mucosal tissues, to prevent recognition of this material by the immune system. Such recognition could result in serious consequences both locally (ie. in the gut) and more distally eg. in the pnacreas leading to diabetes. As a consequence, we believe that these antibodies are fundamental to health. The research could have important ramifications for diseases resulting from immune responses against host tissues, so-called autoimmune diseases like diabetes.Read moreRead less
Mechanism/s Of Disease Caused By Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$479,517.00
Summary
A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract ill ....A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract illness similar to RSV, but with an unknown etiology, suggests that HMPV may mediate similar clinical pathology. Nothing is currently known about the immune response to HMPV, or the association of these responses with lung disease. The objectives of this proposal are to elucidate the mechanisms of immunity and disease pathogenesis associated with human metapneumovirus (HMPV) and to investigate the use of a novel vaccine to protect against HMPV infection. Once this data is obtained, the study will provide the foundation for further research in the development of vaccines or therapeutic protocols to treat HMPV. It will also provide valuable information for understanding the disease in humans. Also,it is likely that HMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less