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.
Increased Vulnerability To Stress During Opiate Dependence: Molecular, Anatomical, And Behavioural Correlates
Funder
National Health and Medical Research Council
Funding Amount
$272,640.00
Summary
Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, s ....Heroin addiction is a major health and societal problem in Australia. It is consistently associated with an adverse impact upon individual users, their families, and communities. It is a chronically relapsing condition for which few, if any effective prevention and treatment strategies exist. Moreover, why an individual initiates and maintains heroin taking remains unclear. Stress and negative emotions have a strong impact on heroin use. Stress may drive some individuals to start using heroin, stress increases the pleasurable effects of heroin and stress increases the aversive effects of heroin withdrawal. These effects will encourage addiction and discourage addicts from seeking treatment. Stress can also cause an otherwise drug-free individual to relapse to heroin addiction despite having been drug-free for some time. In this project we will study why stress has such a large impact on heroin addicts and heroin addiction. We will test the hypothesis that heroin use actually produces profound alterations in the neural network in the brain which controls responses to stress. This project uses a simple animal model of heroin addiction whereby rats are injected with morphine to study the regulation of several genes which are important in responding to stress. We will also study how this exposure and changes in gene expression alter neurobiological, cardiovascular, and behavioural responses to stress. This project will identify parts of the brain that are altered during heroin addiction, and will also identify why heroin addicts are more vulnerable to stress than the general population. Therefore, this project will help us to identify targets for therapeutic intervention (both psychological and pharmacological) and possibly disrupt the addictive cycle.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.
Is Placental Aging The Key To Understanding, Predicting And Preventing Stillbirth?
Funder
National Health and Medical Research Council
Funding Amount
$473,861.00
Summary
Stillbirth occurs in 35 times as many pregnancies as sudden infant death but the causes are unknown. This project will help to develop tests that can predict the risk of stillbirth so that the obstetrician can deliver the baby before it dies. The investigators hypothesise that stillbirth is due to aging of the placenta and that markers of the aging placenta can be detected in the mother’s blood. The project brings together experts in the placenta, aging and obstetric care of high risk pregnancy.
Inhibition Of Fear Memories By Extinction: Neural Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$234,250.00
Summary
Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relati ....Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relatively little is known about the mechanisms by which fear memories can be inhibited or suppressed. Understanding this latter process is a key to the development of effective treatments for anxiety disorders such as PTSD where the patient suffers from persistent, intrusive, unwanted trauma memories. A common experimental procedure for reducing learned fear is to repeatedly expose the subject to a fear-eliciting stimulus but without any aversive outcome. This procedure leads to a progressive loss, or extinction, of the fear reactions elicited by the stimulus. Historically, the extinction of fear was thought to be due to an erasure of the fear memory. However, recent evidence shows that extinction inhibits, rather than erases, the fear memory. Because the fear memories remain intact, some structure(s) in the brain must inhibit activity in the fear pathway. This project uses extinction of conditioned fear reactions in rat subjects to determine the structure(s) in the brain that inhibit fear memories and their behavioural and cardiovascular expression. It brings together the expertise of four well-established researchers and uses a combination of behavioural, physiological, immunohistochemical, tract tracing, and lesion approaches to achieve this aim. The proposed experiments will reveal the structure(s) in the brain that control the inhibition of fear, as well as the site(s) of this inhibition in the fear pathwayRead moreRead less
Neurobiological Causes Of Overeating In A Rodent Model - Hedonic Versus Homeostatic Control
Funder
National Health and Medical Research Council
Funding Amount
$431,215.00
Summary
Unlimited access to palatable high fat foods, in conjunction with a sedentary life style, has led to increased obesity. Exactly what mechanisms drive over consumption of energy rich foods and override mechanisms that normally regulate body weight? This project will examine feeding behaviour in rats fed palatable high fat diet, to examine when and how they eat. The contribution of brain chemicals implicated in addiction to this eating, and the impact of withdrawal of food will be examined.
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
Indigenous Mental Health Model Of Care: RCT Based On A Trans-diagnostic CBT Program Co-designed With Community
Funder
National Health and Medical Research Council
Funding Amount
$996,217.00
Summary
We propose to develop an Indigenous Model of Mental Health Care (IMMHC) that encompasses psychological therapy and cultural healing practices developed in consultation with local, participating Indigenous communities, that will for the first time treat highly prevalent mood and anxiety disorders in Indigenous Australians.