The Role Of Proinflammatory Interleukin-17 (IL-17) And IL-17-producing T Cells In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$470,051.00
Summary
Peripheral nerve injury often results in persistent and debilitating neuropathic pain. My overall objective is to understand the immunological mechanisms responsible for such pain. I plan to test the hypothesis that the proinflammatory cytokine interleukin-17 promotes neuroinflammation and contributes to increased pain sensitivity after nerve injury. This study promises to enhance our understanding of neuroimmune activation in neuropathic pain and offers new opportunities for pain management.
Role Of Synaptogenesis In Developmental Motoneuron Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$361,650.00
Summary
Naturally occurring cell death is an important and necessary event that shapes the developing embryo. It occurs in all organs of the developing body. In the nervous system about 50% of all neurons die at a time when they are making contact with one another or with their target organs. The underlying mechanisms that drive programmed neuronal cell death are not known. One possibility is that the formation of neuronal contacts (synapses) with other neurons and target cells determines the fate of a ....Naturally occurring cell death is an important and necessary event that shapes the developing embryo. It occurs in all organs of the developing body. In the nervous system about 50% of all neurons die at a time when they are making contact with one another or with their target organs. The underlying mechanisms that drive programmed neuronal cell death are not known. One possibility is that the formation of neuronal contacts (synapses) with other neurons and target cells determines the fate of a neuron. The connections of motor neurons with muscle during this period of developmental neuronal cell death is the best model to examine this phenomenon. In this grant we are in an exciting position to be able to address what causes neuronal cell death, as we have a number of mice that lack key molecules needed for the formation of specializations that allow neuronal contacts to be made between motor neurons and their muscle, and with other neurons within the spinal cord. By examining the function of motor neurons, counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism of how a motor neurons' fate is determined during the period of programmed cell death. The outcomes of this research will enable us to understand how the nervous system is shaped during development and will increase our knowledge about the basis of adult neurodegenerative diseases. For example, the pathology of Alzheimer's is characterised by a breakdown in neuronal connections that ultimately result in neuronal death and a loss of thought processes (cognition).Read moreRead less
Pathophysiology Of Focal Human Entrapment Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$33,626.00
Summary
Neuropathy patients suffer from tingling, pain, numbness, spontaneous muscle contraction and cramp. The symptoms reflect abnormal activation of the nerve involved. It is known that an external agitation can worsen them, like in carpal tunnel syndrome (CTS). This study aims to investigate if changes in function of axonal membrane ion channel play any part in the symptoms. This will be done by comparing axonal membrane ion channel functions of healthy and CTS patients under external stimuli.
Effects Of Muscle Inflammation On Sensory Neuron Excitability
Funder
National Health and Medical Research Council
Funding Amount
$397,398.00
Summary
Muscle pain is a common and poorly treated health problem for many Australians. This project examines the properties of nerves that sense muscle pain and looks at how these change during inflammation, a common cause of muscle pain. We are looking specifically at jaw muscles, which are one of the most common sites of chronic muscle pain. By understanding how muscle nerves are changed by injury, we hope to be able to develop treatments to prevent or reverse these changes.
The goal of the proposed Program is to improve treatments forpain, especially persistent pain, which remains a poorly managed global health burden. Our pre-eminent team integrates a unique set of complementary research skills in using peptides derived from venomous invertebrates to dissect the pharmacology of pain pathways in persistent pain states, and develop these novel peptides to the point where they can be considered for pre-clinical development in collaboration with commercial partners.
Prevention Of Neuron Death By Targeted Gene Delivery
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
Neurotrophic factors are potent proteins that have the ability to keep nerves alive. They have therefore been used in clinical trials to treat motor neuron disease, but without success. A major reason for this appears to be the way in which the neurotrophic factors are delivered. Direct injections into the blood stream are a convenient way of getting these large proteins into the bloodstream, but this is not their normal mode of action. These proteins are normally provided by cells adjacent to t ....Neurotrophic factors are potent proteins that have the ability to keep nerves alive. They have therefore been used in clinical trials to treat motor neuron disease, but without success. A major reason for this appears to be the way in which the neurotrophic factors are delivered. Direct injections into the blood stream are a convenient way of getting these large proteins into the bloodstream, but this is not their normal mode of action. These proteins are normally provided by cells adjacent to the nerves. We have designed a system that more closely resembles this physiological mode of action which involves the delivery of neurotrophic factor genes, via the bloodstream, to the affected nerves. Once inside the nerves the factors are produced on site and, following their secretion, act locally and directly on the injured nerves.Read moreRead less
Functional Neuroimaging In Mild Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$176,719.00
Summary
Mild traumatic brain injury (mTBI) represents a significant public health issue in Australian communities. Complications can include prolonged symptoms, depression and progressive deterioration of brain function. Clinical management of mTBI hinges on accurate assessment of recovery. The aim of the current study is to investigate the role of novel functional brain imaging techniques such as diffusion tensor imaging and connectivity studies, in the assessment of brain disturbance following mTBI.
Communication Between Calcium Ion Channels In Skeletal Muscle Excitation-contraction Coupling
Funder
National Health and Medical Research Council
Funding Amount
$603,100.00
Summary
Ageing, injury, drugs or genetic defects cause muscle weakness, prevent exercise, compromise life style and contribute to poor health and osteoporosis. In order to move signals travel from our brain to muscles, where one calcium ion channel detects the signal and tells a second calcium channel to open and release calcium ions to initiate contraction. The project will pave the way for developing drugs to help with muscle disorders by trageting the site of interaction between the channels.
After The Cloning Of The HMSNL Gene: Molecular Pathogenesis Of The Disease
Funder
National Health and Medical Research Council
Funding Amount
$258,564.00
Summary
We have completed an NHMRC-funded study, where we identified the gene for a severe disorder of the peripheral nervous system. The disease, hereditary motor and sensory neuropathy - Lom (HMSNL), presents with gait disturbances, difficulty in using the hands, muscle weakness and wasting and sensory loss. The concomitant impairment of the insulating myelin sheath surrounding nerve fibres (facilitating nerve conduction) and of the nerve fibres themselves suggests that the molecular defect lies in th ....We have completed an NHMRC-funded study, where we identified the gene for a severe disorder of the peripheral nervous system. The disease, hereditary motor and sensory neuropathy - Lom (HMSNL), presents with gait disturbances, difficulty in using the hands, muscle weakness and wasting and sensory loss. The concomitant impairment of the insulating myelin sheath surrounding nerve fibres (facilitating nerve conduction) and of the nerve fibres themselves suggests that the molecular defect lies in the basic mechanisms of interaction between the two main types of cell in the peripheral nervous system: the myelin-producing Schwann cell and the neuron. The two cells form the most complex system of communication in the human body, where signaling from one is vital for the development, functioning and survival of the other. Very little is known about the molecular mechanisms of this communication. At the same time, knowledge of the normal mechanisms of interaction is the key to better understanding of the mechanisms of disease in the peripheral nervous system and of the causes and possible prevention of the impairment of function. The newly identified HMSNL gene is probably involved in the signaling necessary for the development and functioning of the Schwann cell and for the survival of the nerve fibres. To gain an insight into the nature of the signaling cascade, we propose to use several complementary experimental approaches. We will create a mouse model of the human disease, to study its very early stages and subsequent evolution. In parallel, we will use molecular techniques and a yeast model, to identify other steps in the signaling cascade. The NHMRC-funded study will be part of a larger project conducted in collaboration with leading laboratories in the UK and the Netherlands, where other aspects of the molecular basis of the disease and of the role of the new gene will be examined.Read moreRead less