Optimising Combinations Of Calcium Channel Inhibitors For Treatment Of Secondary Degeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$679,772.00
Summary
Traumatic injury to the central nervous system is made worse by damage that spreads away from the initial point of impact. Excess calcium entering cells is a key contributor to spreading damage but treatment with single calcium channel inhibitors has been disappointing. We will use combinations of calcium channel inhibitors to block multiple calcium channels and ensure the optimised combination is effective in clinically relevant models of neurotrauma.
Neuron To Glia Signalling: Learning How Synaptic Signalling Can Promote CNS Remyelination
Funder
National Health and Medical Research Council
Funding Amount
$609,650.00
Summary
An immature cell type in the brain, known as the oligodendrocytes progenitor cell (OPC), receives direct electrical communication from neurons. This communication regulates the behavior of the OPC, affecting its ability to divide and generate new brain cells. This project will identify the signaling molecules that guide the OPC to for this specialized contact with the nerve cell. Understanding this communication has important implications for the treatment of Multiple Sclerosis.
Targeted Nanoparticles To Deliver Combinations Of Calcium Channel Inhibitors To Prevent Myelin Damage During Secondary Degeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$895,244.00
Summary
Following injury to the central nervous system the damage spreads into nearby areas, leading to worse outcomes for the patient. We will generate nanoparticle systems to deliver effective therapies directly to the most vulnerable cells, critical for function. We will modify the nanoparticles so that they can get to the injury site, both early after injury, and after longer periods of time have elapsed. We will then test the nanoparticle systems to see if they are effective at preserving function
Decoding Dysfunctional Spinal Cord Circuitry In Chronic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$516,101.00
Summary
Chronic pain is common, with one in five Australians having long-term pain that is serious enough to cause disability. Unfortunately this type of pain is difficult to treat, and current medicines are ineffective in many people, with unwanted side-effects. The aim of this project is to understand how signalling in the spinal cord changes following the development of chronic pain so we can find better strategies to reverse the symptoms and treat pain more effectively.
The Role Of Action Potentials In Local Calcium Signalling And Induction Of Different Forms Of LTP
Funder
National Health and Medical Research Council
Funding Amount
$330,691.00
Summary
Our understanding of how the brain learns and remembers things is still limited. There is good evidence that changing the strength of the connections (synapses) between brain cells (neurons) can allow information to be stored. One type of synaptic change is called long-term potentiaton (LTP), which is a long-lasting increase in the efficacy of communication between neurons. Recently, I have described 3 different forms of LTP in a region of the brain that is known to be important for learning and ....Our understanding of how the brain learns and remembers things is still limited. There is good evidence that changing the strength of the connections (synapses) between brain cells (neurons) can allow information to be stored. One type of synaptic change is called long-term potentiaton (LTP), which is a long-lasting increase in the efficacy of communication between neurons. Recently, I have described 3 different forms of LTP in a region of the brain that is known to be important for learning and memory. These forms of LTP have different persistence characteristics - LTP 1 is relatively short-lasting, LTP 2 is of intermediate duration, and LTP 3 is very long-lasting and perhaps even permanent. Each form of LTP is selectively triggered by an increase in calcium in a different part of the neuron. In the present study, I will investigate the relationships between electrical activity in different parts of the neuron in order to define the 'rules' for triggering each form of LTP. This information is important for future studies into the specific role played by each form of LTP in learning and memory processing in the brain. A better understanding of the relationship between LTP and learning and memory will assist in developing effective treatment strategies for disorders of memory, including Alzheimer s disease, addictive bahaviour, and learning disorders.Read moreRead less
Investigating Genetic Determinants Of Absence Epilepsy In A Polygenic Rat Model
Funder
National Health and Medical Research Council
Funding Amount
$458,481.00
Summary
The underlying genetic causes of idiopathic generalised epilepsies (IGE) are still largely unknown. In an animal model of IGE we have discovered novel genetic abnormalities an ion channel. This proposal will build upon these novel findings to examine the role these abnormalities have in determining the absence epilepsy phenotype and this work has the potential to provide vital information regarding the mechanisms by which this gene contributes to an IGE seizure phenotype.
Astrocyte-Neuron Communication: Unravelling The Role Of Astrocytes In The Modulation Of Neuronal Circuits
Funder
National Health and Medical Research Council
Funding Amount
$403,064.00
Summary
Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neur ....Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neurodegenerative states (e.g. Alzheimer's disease, Parkinson's disease, and multiple sclerosis). Many of these diseases are associated with a pathological astrocyte process known as 'reactivity'. This process remains enigmatic, resulting in so-called reactive gliosis, a reaction characterized by changes in gene expression, cell enlargement and changes in cell shape, and, in some cases, cell division. Most of the research on astrocyte reactivity has focused on the impairment of astrocyte metabolic activities. Comparatively little is known about the effect of reactive gliosis on so called 'newer' astrocyte roles such as their ability to interact with each other and nearby neurons using exocytosis of gliotransmitters (GTs: glutamate and ATP) and neurotrophic factors (NTFs: glial and brain derived neurotrophic factors). This project will both further investigate the normal mechanisms of astrocyte-neuron communication, and examine the effects of astrocyte reactivity on these mechanisms. The aim is to identify possible therapeutic targets to ameliorate the detrimental affects of neurodegeneration.Read moreRead less
Repair Of The Nigrostriatal Pathway By Phenotype Shift Of Dopamine Neurones
Funder
National Health and Medical Research Council
Funding Amount
$561,558.00
Summary
Repairing the injured brain will depend on developing new cells that can form the correct cell type, make the right connections and be incorporated into normal brain circuitry. We have found that dopamine cells, which are lost in Parkinson's Disease, are being renewed in the adult rodent brain. This study is directed at finding factors that control this process and to exploit these factors therapeutically. We provide evidence that this can be used to treat Parkinson's Disease.