Do Changes In HCN Channels Function Cause Epilepsy?
Funder
National Health and Medical Research Council
Funding Amount
$386,172.00
Summary
About 100 000 people suffer from epilepsy in Australia with about one third poorly controlled with current anti-epileptic drugs. It is important to continue to develop novel modes of treatment for this debilitating disease. This project investigates an ion channel, known as HCN that is thought to be involved in making a brain epileptic. Understanding how changes in HCN channels make nerve cells and nerve networks more excitable will help us develop better strategies for designing drugs.
The Effect Of Stress And Hypercortisolaemia On Limbic Epileptogenesis & Affective Disorder.
Funder
National Health and Medical Research Council
Funding Amount
$380,714.00
Summary
This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is ....This project has the potential to provide novel insights about the causal connections between stress, psychiatric illness (specifically anxiety and depression) and temporal lobe epilepsy (TLE) - the most common form of medical refractory epilepsy in the community. Up to 50% of patients with TLE suffer from anxiety and-or depression. Until relatively recently it had been widely assumed that this was a consequence of the chronic epileptic condition. However, recent evidence suggests that there is a bi-directional relationship, with the psychiatric conditions and stress also acting to aggravate the seizures and even predispose to the development of the epilepsy itself. Apart from gaining insights into causes of TLE, anxiety and depression, this framework has potential public health relevance suggesting approaches to the eventual primary and secondary prevention of both MTLE and its associated psychiatric co-morbidities, a neglected area at present. The use of an animal model allows investigation of aetiological processes that extend over the lifetime, which is exceptionally difficult to achieve in humans. Retrospective studies, such as case-control studies, although an indispensable research methods, are subject to bias and imprecision when it comes to measuring remote past exposures to stress, abuse, and deprivation. If the results of these experiments are consistent with our hypotheses, a very strong case would exist for exploring this relationship in human studies. The data would also provide a strong rationale for more aggressive detection and treatment of these psychiatric co-morbidities in TLE patients, in order to potentially modify the progression of the disorder as well as improve the quality of life of sufferers. The results of intervention studies in animal models may suggest specific mode of treatment to achieve this.Read moreRead less
Why Does Early Life Stress Aggravate Limbic Epileptogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$540,116.00
Summary
High rates of anxiety and depression occur in individuals with temporal lobe epilepsy (TLE), the most common form of focal epilepsy in adults. Rats that have experienced early life stress show increased anxiety, decreased seizure thresholds and accelerated epilepsy as adults. We have important leads to mechanisms. The proposed study will better understand the mechanisms connecting early life stress and psychiatric disease to adult TLE, and to test interventions that may counteract these effects.
Temporal Processing In The Superior Olivary Complex: Impact Of Deafness And Peripheral Electrical Stimulation Strategies
Funder
National Health and Medical Research Council
Funding Amount
$225,500.00
Summary
The brain can use timing or temporal information to extract the frequency and location of sound. Timing information is coded by the pattern of responses of brain cells that match the period of the sound wave. These responses can be measured as small voltage spikes or action potentials. Integration of these responses from one brain-processing site to another relies on precise (temporally matched) firing among a population of cells that are activated in response to sound. Sound localisation relies ....The brain can use timing or temporal information to extract the frequency and location of sound. Timing information is coded by the pattern of responses of brain cells that match the period of the sound wave. These responses can be measured as small voltage spikes or action potentials. Integration of these responses from one brain-processing site to another relies on precise (temporally matched) firing among a population of cells that are activated in response to sound. Sound localisation relies on this temporal integration from information coming from both ears. Specifically, the integration of this information relies on the balance of incoming inputs from both ears, which maintains an appropriate time window depending on the location of sound in space. Recent evidence suggests that in deafness this process of integration is disrupted which may be possibly due to an inability to regulate the coherent activation of cells. This has implications for cochlear implant users whose ability to process temporal information is compromised by a loss of temporal coding ability resulting from prior deafness. In this project we will measure voltage changes occurring inside cells of the superior olivary complex, which contains a group of structures that integrate input from both ears. We will examine the ability of these cells to process temporal information in normal and deafened conditions. This study will lead not only to an understanding of basic mechanisms for auditory coding but also to improved electrical stimulation strategies for patients with cochlear implants.Read moreRead less
Altered HCN Channel Expression And Function In Acquired Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$279,912.00
Summary
About 100 000 people currently suffer from epilepsy in Australia and of these about one third are poorly controlled with current anti-epileptic drugs. It is therefore important to continue to develop novel modes of treatment for this debilitating disease. This projects investigates an ion channel, known as the HCN channel, that is thought to be involved in making a brain epileptic. We explore how changes in this channel can make a brain more excitable. Also, our group is the first in the world t ....About 100 000 people currently suffer from epilepsy in Australia and of these about one third are poorly controlled with current anti-epileptic drugs. It is therefore important to continue to develop novel modes of treatment for this debilitating disease. This projects investigates an ion channel, known as the HCN channel, that is thought to be involved in making a brain epileptic. We explore how changes in this channel can make a brain more excitable. Also, our group is the first in the world to discover a mutation in this channel that is linked to epilepsy. We will also investigate how this mutation changes the channel properties to make a brain more likely to be epileptic. The HCN channel is an important target for developing anti-epileptic drugs. Understanding how changes in HCN channels make nerve cells and therefore nerve cell networks more excitable will help us develop better strategies for designing anti-epileptic drugs.Read moreRead less