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Neurosteroid Mediated Protection After Birth: Approaches For Maximising Protective Steroid Levels In The Neonatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$450,703.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the ....Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the fetal brain and levels rise further in response to fetal stress. The placenta contributes steroid precursors that help maintain these high neurosteroid levels. This placenta-fetal brain interaction comprises an internal mechanism that protects the fetal brain from adverse events during pregnancy. At birth, however, there is a dramatic decline in neurosteroid concentrations in the brain after the loss of the placental precursor supply. The fall in concentrations is even greater in animals that are born growth restricted. This suggests that newborns, particularly those from compromised pregnancies, are at increased risk of brain damage due to low neurosteroid levels. We believe that certain commonly used steroid therapies may also lower steroid levels in the brain and result in increased vulnerability to brain damage during birth or in the early neonatal period. Alternatively, we propose that replacement of neurosteroid precursors in the newborn may raise brain neurosteroid levels and protect against brain damage. In the proposed studies we will evaluate treatments that can raise the concentration of steroids and determine the best strategy for reducing brain injury following complications during pregnancy, at birth and during the early newborn period. This work will determine the best therapeutic approaches for maximising neurosteroid-induced brain protection and for reducing the risk of brain damage.Read moreRead less
Pathways Of Neurosteroid-mediated Protection Following Compromised Pregnancy And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$565,785.00
Summary
The hormonal environment of pregnancy is essential for normal development of the fetal brain. Levels of key hormones fall following premature birth and are further suppressed if the fetus is small or subjected to stress. This leads developmental problems in infants from the pregnancies. This project will examine effectiveness of replacement and supplementation treatments with critical neurosteroid hormones in reversing the adverse neurological effects of these complications of pregnancy.
Reducing The Effects Of Antenatal Alcohol On Child Health (REAACH)
Funder
National Health and Medical Research Council
Funding Amount
$2,497,397.00
Summary
Use of alcohol in pregnancy can affect the developing baby and cause Fetal Alcohol Spectrum Disorders (FASD). Children with FASD have lifelong brain injury that can lead to poor school performance, poor mental health and trouble with the law. This CRE builds on our strong background in research and community engagement to improve FASD prevention, diagnosis and treatment across Australia.
Neuroactive Steroids In The Developing Brain: Potential For Preventing Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown tha ....Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown that protective neuroactive steroids are present in very large amounts in the fetal brain. Steroids produced by the placenta are converted to these neuroactive products by enzymes in the brain leading to the high levels that are seen during fetal life. Certain adverse conditions during pregnancy as well as preterm birth may cause marked changes in the balance of steroids that could increase susceptibility to brain injury. We have found that areas of the brain, where damage most often occurs, normally contain the highest amount of protective steroids, but only in late pregnancy. This suggests that disturbances that lower steroid production in these areas could contribute to the death of cells, particularly in mid-pregnancy and after premature birth. In the proposed studies, we will examine whether a toxic balance of steroids develops following adverse events in pregnancy as well as the areas of the brain where this is most pronounced. We will examine the changes in the expression of enzymes that can potentially cause the accumulation of protective steroids in the brain. We will then examine treatments that can raise the concentration of steroids and determine which combination of steroids best reduces cell death and brain injury following complications during pregnancy. The findings of this work will indicate the best therapeutic approach that may be adopted to modify the concentration of certain steroids so as to reduce the risk of brain damage in the fetus and neonate.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190101364
Funder
Australian Research Council
Funding Amount
$422,460.00
Summary
Securing future supplies of chicken-meat protein. This project aims to generate advanced knowledge in amino acid metabolism in poultry in order to reduce soybean inclusion in broiler diets. Chicken-meat is the dominant animal protein source in human diets in Australia. However, Australia chicken-meat industry will need to increase production by more than 40 per cent to meet population growth by 2050. Soybean meal is the major protein source in poultry diets but the sustainability of increased so ....Securing future supplies of chicken-meat protein. This project aims to generate advanced knowledge in amino acid metabolism in poultry in order to reduce soybean inclusion in broiler diets. Chicken-meat is the dominant animal protein source in human diets in Australia. However, Australia chicken-meat industry will need to increase production by more than 40 per cent to meet population growth by 2050. Soybean meal is the major protein source in poultry diets but the sustainability of increased soy production is problematic. The expected outcomes of this project will be an increase in our future capacity to produce affordable, healthy chicken-meat with humane animal welfare by novel dietary formulations. Chicken-meat production generates less greenhouse gases than its competitors but this project will contribute to the reduction of harmful environmental outputs and ensure food security for Australia.Read moreRead less
Manipulation of the growth potential and carcass composition of domestic animal species. Finding alternatives to repeated growth hormone(GH) injection to boost production efficiency and minimise carcass fatness remains an important target for animal research. This application exploits the two novel approaches to achieve this goal through: 1. the administration of the GH releasing peptides to the neonate to imprint an enhanced GH secretory pattern and feed conversion efficiency during growth ....Manipulation of the growth potential and carcass composition of domestic animal species. Finding alternatives to repeated growth hormone(GH) injection to boost production efficiency and minimise carcass fatness remains an important target for animal research. This application exploits the two novel approaches to achieve this goal through: 1. the administration of the GH releasing peptides to the neonate to imprint an enhanced GH secretory pattern and feed conversion efficiency during growth to maturity and 2. the development of an orally active form of these peptides by conjugation with VitB12 to facilitate intestinal absorption through the VitB12 transport mechanism for delivery to the hypothalamic/pituitary axis of animals nearing maturity.Read moreRead less
A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a proces ....A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a process that enables single cells to respond to molecules sent from a distance by other cells (TGF-beta signalling). This process is also very important for a host of other biological processes relevant to human health, including cancer.Read moreRead less
Development of a non-invasive diagnostic test of Embryo Viability. A successful outcome will:
. improve the cost effectiveness of assisted reproductive technologies resulting in reduced health care costs and allowing greater use of ART in animal production
. by greater cost-effectiveness, facilitate greater access to these advanced technologies in less well developed economies
. build the national capacity in development and validation of biotech diagnostics
. build collaborative relationsh ....Development of a non-invasive diagnostic test of Embryo Viability. A successful outcome will:
. improve the cost effectiveness of assisted reproductive technologies resulting in reduced health care costs and allowing greater use of ART in animal production
. by greater cost-effectiveness, facilitate greater access to these advanced technologies in less well developed economies
. build the national capacity in development and validation of biotech diagnostics
. build collaborative relationship between the CI, University of Sydney and a leading industry partner (Cook Australia)
. lead to significant new fundamental knowledge in embryology that will be of major International significance
Read moreRead less
A Dietary Intervention In Gestational Diabetes To Reduce Child Obesity: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$354,715.00
Summary
Women with gestational diabetes (GDM) whose blood glucose levels (BGL) are not well controlled have a higher chance of giving birth to large babies. These babies are at high risk of becoming overweight children and adults. Preventing child obesity therefore requires appropriate intervention during pregnancy complicated with GDM. This study will determine the ability of specific dietary advice (aimed at reducing maternal BGL) to reduce the risk of large babies in a typical ante-natal setting.