Understanding Local And Regional Determinants Of EDHF And NO Dysfunction In Resistance Arteries In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$771,295.00
Summary
Diabetes is a serious and increasing health burden worldwide. Most of the sickness and death associated is due to complications arising in the blood vessels. The inner lining of blood vessels in small arteries uses several different mechanisms to ensure proper blood flow, and in diabetes these are impaired. This study will reveal the cellular mechanisms involved and identify pathways for therapeutic intervention to alleviate the debilitating effects of small artery disease.
Effect Of Pregnancy And Pre-eclampsia On Smooth Muscle And Endothelial Cell Function In Arteries Isolated From Women
Funder
National Health and Medical Research Council
Funding Amount
$194,537.00
Summary
During normal pregnancy the blood vessels of the mother become relaxed. This helps to meet the growing demands of the mother at this time and also ensures sufficient blood supply to the developing fetus. Blood vessels are lined by a single cell layer called the endothelium. The endothelium inactivates a variety of circulating agents which cause arteries to contract, and it also produces potent substances that directly relax the muscle cells in the blood vessel wall. Thus the endothelium plays an ....During normal pregnancy the blood vessels of the mother become relaxed. This helps to meet the growing demands of the mother at this time and also ensures sufficient blood supply to the developing fetus. Blood vessels are lined by a single cell layer called the endothelium. The endothelium inactivates a variety of circulating agents which cause arteries to contract, and it also produces potent substances that directly relax the muscle cells in the blood vessel wall. Thus the endothelium plays an important role in the adaptation of the maternal blood vessels to pregnancy. Insufficient blood supply to the placenta somehow triggers myriad processes including endothelial dysfunction, enhanced clotting of the blood and contraction of the maternal blood vessels, which culminates in the serious disorder of pregnancy known as pre-eclampsia. This condition threatens the health of both mother and fetus, and in Australia, is responsible for 15% of direct maternal deaths and 10% of perinatal mortality. The focus of this project is to study the function of the endothelium and the muscle in the artery wall, and how the function of these entities is altered in the natural adaptation to pregnancy and in pre-eclampsia. The general aim of this study is two fold: (1) to determine how endothelial function adapts to pregnancy and how this is compromised in pre-eclampsia (2) to determine how factors released from the endothelium alone, or in combination with changes in inherent muscle function, alter the state of relaxation and contraction of muscle in the blood vessel wall, and the influence of pregnancy and of pre-eclampsia on these. This project will contribute to a greater understanding of the mechanisms that control the relaxation and contraction of blood vessels in normal pregnancy and those mechanisms that are impaired during pre-eclampsia and thus, may facilitate the development of treatments for this serious disorder.Read moreRead less
Studying The Two Hit Hypothesis Of Psychiatric Illness: Role Of Brain-derived Neurotrophic Factor (BDNF)
Funder
National Health and Medical Research Council
Funding Amount
$314,034.00
Summary
Psychiatric illnesses such as schizophrenia and depression are caused by at least two major disrupting events in development: one during early brain development and one during-after puberty. We will use animal models of schizophrenia, induced by administering stressors such as maternal separation, corticosterone or cannabinoid treatment at different stages of their lives. These animal models will be used to further investigate antipsychotic treatment therapies
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.
A Multi-cohort Investigation Of The Effects Of BDNF Val66Met On Tau, Neurodegeneration And Cognition In Preclinical Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$325,758.00
Summary
There are currently no disease modifying therapies for Alzheimer’s disease. We will elucidate the role of a genetic polymorphism that has previously been shown to exert neuroprotective effects on memory decline and brain volume loss associated with Alzheimer’s disease. By studying the role of this gene in multiple cohorts of individuals with varying degrees of Alzheimer’s disease risk, this study has high potential to uncover novel disease-modifying strategies for the treatment of the disease.
Analysis Of Functional Role Of The BDNF Precursor In Sensory Neurons
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Neurotrophins, which are generated from their precursors, are essential for the survival and function of the nervous system. One of neurotrophins, brain derived neurotrophic factor (BDNF), is made in sensory neurons and transported towards nerve terminals. Mutation of a single amino acid in the precursor of BDNF disrupts this transport. This project will examine whether the precursor of BDNF has any function within sensory nerves. We will examine whether the precursor of BDNF gets into the nerve ....Neurotrophins, which are generated from their precursors, are essential for the survival and function of the nervous system. One of neurotrophins, brain derived neurotrophic factor (BDNF), is made in sensory neurons and transported towards nerve terminals. Mutation of a single amino acid in the precursor of BDNF disrupts this transport. This project will examine whether the precursor of BDNF has any function within sensory nerves. We will examine whether the precursor of BDNF gets into the nerve via its receptors and whether it plays any role in the development of pain and maintenance of neuropathic pain after nerve injury. Successful execution of the project will eludicate mechanisms of pain, especially neuropathic pain, and will provide important information to assist in the design of drugs for neurological diseases.Read moreRead less
BDNF Genotype And Emotional Memory In Post-traumatic Stress Disorder
Funder
National Health and Medical Research Council
Funding Amount
$108,902.00
Summary
This project addresses the question of why some people develop PTSD following trauma and others don’t. It will assess the influence of genetics (specifically a genotype that influences Brain Derived Neurotrophic Factor) on emotional memory processes as distressing emotional memories are a core symptom of PTSD. If we find that people with a particular genetic profile have a greater risk of developing intrusive memories after trauma, this will help us better target treatment for those individuals.
Roles Of Brain-derived Neurotrophic Factor In The Regulation Of Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$299,625.00
Summary
Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to ....Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to analyse physiological roles of BDNF in the brains stem and spinal cord in the regulation of nerve activity and blood pressure. The successful execution of the project will significantly enhance our understanding of how blood pressure is controlled by BDNF and nerve activity. The knowledge from this study will form basis for designing new drugs to control high blood pressure.Read moreRead less