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
Novel Strategies To Promote Myelin Repair In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$597,865.00
Summary
Demyelinating diseases of the central nervous system such as multiple sclerosis have a lifelong impact and devastating impact on quality of life. We have identified that a growth factor, brain derived neurotrophic factor (BDNF), plays an important role in promoting myelination during development. We will investigate the potential of translating these findings into effective clinical treatment, by characterising the efficacy of BDNF in promoting CNS remyelination after a demyelinating insult.
Differential Changes In Cortical Tumour Necrosis Factor Signalling In Mood Disorders And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$642,078.00
Summary
Changes in inflammation-related pathways contribute to the symptoms of psychiatric disorders and tumour necrosis factor ? (TNF) is a protein central to regulating theses pathways. We have now shown that changes in pathways regulated by TNF are present in the brains of people with schizophrenia and mood disorders. This means that the symptoms experienced by those with the different disorders may be linked to differential changes in TNF-regulated pathways in the brain.
Which Neurons Maintain Sympathetic Vasomotor Tone?
Funder
National Health and Medical Research Council
Funding Amount
$567,918.00
Summary
High blood pressure is a major risk factor for cardiovascular disease, a major burden of disease worldwide. High levels of nerve activity that cause the blood vessels to constrict elevating blood pressure are characteristic of hypertension. We do not know which brain cells set and maintain this nerve activity. We will identify these cells, determine how they function and what regulates them. Ultimately we could control these cells treating the cause of hypertension or when clinical need arises.
The Role Of BDNF In Central Nervous System Myelination
Funder
National Health and Medical Research Council
Funding Amount
$478,235.00
Summary
Multiple Sclerosis (MS) is the most common neurological cause of disability in young adult Australians. The cause of MS is unknown and therapies are limited to reducing inflammation, which does not address the major problem of the disease: loss of myelin. This project directly investigates how myelin is formed and will identify key mechanisms in this process, which may eventually be developed into treatments for diseases such as MS.
Viral-mediated Modulation Of BDNF Expression In Motor Neurons To Promote The Recovery Of Hand/digits Function In A Rat Model Of Spinal Cord Injury That Impairs Normal Grasping Action.
Funder
National Health and Medical Research Council
Funding Amount
$341,427.00
Summary
This project seeks to lure injured axons towards motor neurons, a process that is essential for the recovery of motor function. BDNF gradients will be created along the injured axons path. Axons will have to elongate to reach the first source of BDNF. They will need to elongate even more to get to the next source of BDNF, hence bringing them each time closer to their lost targets. This gene therapy scenario has the potential to bring gene therapy a step closer for human spinal cord injury.
The Combined Use Of Transplantation And Gene Therapy Techniques To Promote Regeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$521,026.00
Summary
Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce gen ....Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce genes into cells, a method that allows targeted supply of molecules to the injured brain. Gene and cell therapy may eventually be of clinical benefit to injured patients. In a range of different experiments we will combine two different gene therapy approaches, various pharmacological agents and novel transplantation strategies in attempts to enhance the survival of affected nerve cells and promote the regrowth of damaged nerve fibres across injury sites in the injured adult rat visual system. Long-term vector-mediated expression of growth factors in neurons and in grafts may 'trap' regenerating axons, potentially reducing their outgrowth into distal, denervated target areas. It is therefore important to determine if temporal regulation of growth-promoting genes has additional beneficial effects on the ability of regenerating neurons to recognise and selectively regrow axons into appropriate CNS targets. An additional series of studies will thus be undertaken. We will test a new generation of regulatory vectors in which it is possible to switch the virally encoded genes on or off and thus control the level and timing of gene expression over a therapeutic range. We will then determine if the use of these regulatory viral vectors results in more consistent and robust growth of nerve fibres with better reconnections, in the longer term leading to better recovery of function.Read moreRead less