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.
THE NEUROBIOLOGICAL BASIS OF INDIVIDUAL DIFFERENCES IN SUSCEPTIBILITY TO THE CONSEQUENCES OF STRESS
Funder
National Health and Medical Research Council
Funding Amount
$583,875.00
Summary
Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those t ....Stress plays a major role in the development and progression of many different mental health disorders. However, as we all know, the effects of stress on one person can be very different from its effects upon another. This is at least partly explained by differences in individual coping styles. When faced with a stressful situation without a ready solution, people tend to divide into two broad camps: those with an innate tendency to adopt passive coping strategies, such as avoidance, and those that tend towards active coping strategies, such as attempting to take control of the situation. Previous studies have provided findings that suggest that passive coping is more common amongst sufferers of depression, post-traumatic stress disorder, and chronic pain syndrome than is active coping. But is this cause, or effect? And what are the intervening brain mechanisms? We attempt to address such questions in the present project using an animal model in which social conflict has been shown to trigger depression-like symptoms. In particular we wish to: (i) determine whether the patterns of brain activity triggered by social conflict are different for active vs. passive copers; (ii) determine whether the depression-like consequences of social conflict are more severe in passive than in active copers; (iii) determine whether differences in coping style and vulnerability to social conflict stress are due to the actions of a particular neurotransmitter, dopamine, in the prefrontal cortex of the brain; (iv) determine whether the actions of antidepressants might be attributable changes in prefrontal cortex dopamine function which in turn promote active coping in preference to passive coping. These studies will provide exciting new information about the neurobiological basis of individual differences in vulnerability to the harmful effects of stress, and thus will offer the hope of developing new ways of preventing devastating illnesses such as depression.Read moreRead less
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.
Innovative And Multi-disciplinary Treatment Strategies For Secondary Degeneration Following Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$455,452.00
Summary
Following injury to the central nervous system the damage spreads into nearby areas, leading to worse outcomes for the patient. The research conducted during this Fellowship will ensure that promising treatment strategies to prevent spreading damage are used in the best way, and will determine the mechanism of action of these treatments.
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.
Harnessing The Human Postmortem Brain To Elucidate Changes In FK506 Binding Protein (FKBP5) In The Neuropathology Of Severe Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$392,052.00
Summary
The postmortem human brain is a unique source to search for the pathological basis of severe psychiatric disorders including major depression, bipolar disorder and schizophrenia. Postmortem tissues are however being underutilised. This project will apply a selection of powerful biochemical measuring techniques to postmortem human brain tissues to uncover the molecular pathways of severe psychiatric disorders, which is knowledge that can lead to better treatments, preventions and cures.