THE EFFECT OF STRESS AND ENVIRONMENTAL ENRICHMENT ON DISEASE PROGRESSION IN MESIAL TEMPORAL LOBE EPILEPSY
Funder
National Health and Medical Research Council
Funding Amount
$578,201.00
Summary
Mesial temporal lobe epilepsy, the most common form of drug-resistant epilepsy in adults, is a progressive neurodegenerative condition for which there is currently no effective disease modifying treatment. This proposal will explore whether co-morbid stress accelerates disease progression in MTLE, and whether targeting stress pathways by medical and environmental manipulations can mitigate against this.
Does Obesity Have The Characteristics Of Addiction?
Funder
National Health and Medical Research Council
Funding Amount
$430,832.00
Summary
The number of overweight or obese people in Australia has increased dramatically in recent years, increasing disease risk. The brain responds to palatable food in ways similar to the response to drugs of addiction, and this may explain why people find it hard to resist palatable food. Our work will explore whether obesity in rats has the characteristics of addiction by examining bingeing, craving, withdrawal and brain circuits in animals chronically exposed to palatable food.
Motivational drive and reward are survival processes that underpin the maintenance of homeostasis. In humans, dysregulation of these brain circuits manifests in disorders such as depression and addictions. Our projects is focused on a key subgroup of neurons in the hypothalamus that modulates reward and motivation. We aim to understand how potent reward experience (e.g. drugs) or stress modifies these circuits and to identify potential entry points for therapeutic interventions.
Transgenerational Impacts Of Paternal Stress On Offspring Mental Health: Epigenetic Mechanisms And Therapeutic Interventions
Funder
National Health and Medical Research Council
Funding Amount
$572,941.00
Summary
We are following up the extraordinary, almost ‘Lamarckian’, discovery that environmental influences on fathers can affect their offspring via ‘epigenetic’ changes to the sperm. We will explore mechanisms whereby increased levels of paternal stress can cause behavioural changes in the offspring, which are relevant to depression and anxiety disorders, and how positive environmental factors, including physical activity, may induce beneficial effects. This will have major public health implications.
Validating Novel Biomarkers Relevant To Major Depression
Funder
National Health and Medical Research Council
Funding Amount
$515,550.00
Summary
Depression prevention and treatment are public health priorities; therefore, it is critical to improve and personalise treatments, which can only be achieved by advancing knowledge of its underlying biology. This research project will contribute to validating potentially relevant genes for MDD risk or antidepressant response and to provide the scientific foundation for future strategies to test their products as MDD biomarkers in the clinical setting.
Microglia As Primary Drivers Of Stress-induced Changes In Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$475,781.00
Summary
Persistent exposure to stressful events can produce serious and lasting disturbances in cognitive function. Our research group has recently identified that microglia may play a very significant role in these disturbances. The studies to be undertaken in this proposal will provide fundamental knowledge on how microglia contribute to neuronal plasticity, and how microglia via their effects on neurons regulate complex cognitive behaviour.
How The Lateral Habenula Integrates Behavioral And Autonomic Functions: The VTA Dopamine Connection
Funder
National Health and Medical Research Council
Funding Amount
$819,904.00
Summary
When adverse events occur, the lateral habenula, an old brain nucleus, helps calculate the wisest corrective action by contributing to the “brake” that controls the brain’s dopamine reward system. Our research will show how the lateral habenula links corrective changes in behavior with coordinated changes in temperature. Understanding this link will greatly contribute to understanding the brain mechanisms that regulate our physiology during stressful situations and as part of mental illness.
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.
Huntington’s disease (HD) is a devastating neurodegenerative disorder which shares several features with Alzheimer’s and Parkinson’s disease (i.e. dementia-like cognitive deficits). There is currently no cure for HD. Using a mouse model of HD and a combination of relevant drugs (i.e. N-Acetylcysteine and deferiprone) targeting two distinct levels of the cascade of events leading to HD, we will slow down the progression of the disease and correct dysfunctions within the brain.
Traumatic Brain Injury, Post Traumatic Stress Disorder And The Risk Of Neurodegenerative Disease: A Study Of Tau And Beta-amyloid Accumulation, Brain Structure And Function Several Decades After Injury.
Funder
National Health and Medical Research Council
Funding Amount
$1,076,860.00
Summary
The study aims to better understand the association between traumatic brain injury (TBI), post traumatic stress disorder (PTSD) and dementia, specifically Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). The study will examine retired AFL players, road trauma victims and Vietnam veterans with advanced imaging using PET brain scans for the abnormal brain deposits typical of AD and CTE and assess the risk of later developing these diseases from head injury and PTSD.