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Exercise Reverses Cognitive Decline In Aged Animals By Growth Hormone Stimulation Of Neurogenesis In The Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$696,409.00
Summary
The production of new neurons in the hippocampus plays a critical role in learning and memory. With increasing age, this production slows and is associated with cognitive decline. However the stem cells that make new neurons are still present, and we have discovered that exercise activates these cells, leading to renewed neuron production and reversal of cognitive decline. We will explore how this process is regulated in order to develop strategies to reduce cognitive decline in humans.
Stimulation Of Neurogenesis By Growth Hormone To Improve Cognition In An Aged Animal Model Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$550,828.00
Summary
Production of new neurons in the hippocampus of adult animals plays a role in regulating learning and memory, and this production slows continuously with increasing age. Here we explore ways to activate dormant populations of neurogenic precursor cells in the hippocampus to produce new neurons. Since the precursor cells are still present in the hippocampus of an aged animal these studies will provide unequivocal evidence for their importance in reversing age-related cognitive decline and dementi ....Production of new neurons in the hippocampus of adult animals plays a role in regulating learning and memory, and this production slows continuously with increasing age. Here we explore ways to activate dormant populations of neurogenic precursor cells in the hippocampus to produce new neurons. Since the precursor cells are still present in the hippocampus of an aged animal these studies will provide unequivocal evidence for their importance in reversing age-related cognitive decline and dementia.Read moreRead less
Novel Interplay Of Oestrogen And Growth Hormone In Regulating Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
These studies provide insights into the mechanisms and role of oestrogen in regulating whole body and liver fat metabolism. Oestrogen-related medications that modify the action or tissue availability of oestrogen are widely used therapeutics and can predispose to obesity and fat accumulation in the liver. Whether the effect is direct or through interplay with other metabolic hormones is unknown. This proposal examines their metabolic consequences and impact on obesity and liver health.
Mechanism Of Activation Of JAK2 By A Class 1 Cytokine Receptor
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Cytokine receptors regulate key processes such as red/white blood cell formation, stature, adiposity and lactation. They use JAK kinases to signal to regulated genes. Here we will use sophisticated technologies able to observe single molecules and crystallography to uncover the mechanism used by these receptors to signal into the cell using a well characterised, simple cytokine receptor, the growth hormone receptor.
Role Of STAT5 In Defining Lifespan In Mouse Models
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
We seek to elucidate the molecular basis for the extended lifespan seen in the Methuselah mouse, the longest lived mouse model of ageing. This mouse lacks the receptor for growth hormone, and we have identified a major gene-regulating protein activated by the growth hormone receptor as correlating with lifespan. This project seeks to establish if this protein does indeed regulate lifespan, and to determine how it does this, particularly in relation to metabolism of toxins and free radicals.
Roles Of The Nuclear Growth Hormone Receptor In Cell Proliferation And Survival
Funder
National Health and Medical Research Council
Funding Amount
$429,387.00
Summary
We have discovered that the cell surface receptor for growth hormone travels to the cell nucleus in dividing cells, including cancer cells. Given the role of growth hormone in promoting growth postnatally, we seek to uncover how the nuclear receptor promotes proliferation directly, and by gene splicing. We have identified strong candidates for its direct actions through proteomics, and a DNA binding site for the receptor. Here we will investigate its role in proliferation, gene splicing and DNA ....We have discovered that the cell surface receptor for growth hormone travels to the cell nucleus in dividing cells, including cancer cells. Given the role of growth hormone in promoting growth postnatally, we seek to uncover how the nuclear receptor promotes proliferation directly, and by gene splicing. We have identified strong candidates for its direct actions through proteomics, and a DNA binding site for the receptor. Here we will investigate its role in proliferation, gene splicing and DNA strand break repair after cell irradiation.Read moreRead less
Functional Analysis Of A Novel Genetic Mouse Model For Congenital Growth Hormone Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$519,131.00
Summary
Pituitary Hormone deficiency is not uncommon and is associated with poor growth, metabolism and fertility. Some cases of this disorder arise due to genetic changes that compromise the ability of the pituitary gland to make or secrete growth hormone (GH). Using cutting-edge genomics technology, we have generated a new genetic mouse model of GH deficiency. The aim of this project is to understand the function of this novel GH _regulating gene in mice and in humans.
Hormone Transport By Alpha-2-Macroglobulin: Novel Roles In Regulating Hormone Activity
Funder
National Health and Medical Research Council
Funding Amount
$602,857.00
Summary
Alpha-2-macroglobulin is a large protein in the blood known to bind and transport numerous hormones in the circulation. Our previous studies published in BLOOD (2009) and JBC (2013) have discovered an important role for this molecule in the transport and regulation of a peptide hormone. The studies proposed in this application have important implications for understanding new roles of alpha-2-macroglobulin in hormone binding and regulating the activity of hormones in disease states.
Regulation Of Growth Hormone Profile By Metabolic Balance: Neuronal, Neuroendocrinal And Molecular Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$413,257.00
Summary
Obesity is associated with a reduction in growth hormone secretion. As growth hormone maintains muscle mass at the expense of fat this may further promote the obese condition. This project will determine the physiological role of ghrelin, a hormone that signals hunger, in maintaining growth hormone secretion under normal, fasting and obese conditions. Clarification of the role of ghrelin in regulating growth hormone secretion may aid in the development of pharmacological agents to assist and mai ....Obesity is associated with a reduction in growth hormone secretion. As growth hormone maintains muscle mass at the expense of fat this may further promote the obese condition. This project will determine the physiological role of ghrelin, a hormone that signals hunger, in maintaining growth hormone secretion under normal, fasting and obese conditions. Clarification of the role of ghrelin in regulating growth hormone secretion may aid in the development of pharmacological agents to assist and maintain weight loss.Read moreRead less