Investigation Of The Mechanisms Involved In Consolidation Of Memory By Beta 3 Adrenoceptoragonists.
Funder
National Health and Medical Research Council
Funding Amount
$241,018.00
Summary
The inability to form new memories is a major and increasingly prevalent health problem for an aging population. In addition to aging, the inability to form new memories is associated with serious medical conditions including Alzheimer's Disease and diabetes. Common to these conditions is the inability to consolidate memories. Memories are intact for a short while (30 minutes) after the event to be remembered, but memory does not pass on into permanent storage. We have been able to achieve memor ....The inability to form new memories is a major and increasingly prevalent health problem for an aging population. In addition to aging, the inability to form new memories is associated with serious medical conditions including Alzheimer's Disease and diabetes. Common to these conditions is the inability to consolidate memories. Memories are intact for a short while (30 minutes) after the event to be remembered, but memory does not pass on into permanent storage. We have been able to achieve memory consolidation in a particular learning task, which is not normally remembered, by injection of drugs acting on novel receptors (beta 3 adrenoceptors) in the brain of day old chicks. These drugs mimic the action of noradrenaline at beta-3 adrenoceptors. There are a number of ways in which memory consolidation can be enhanced, and we will compare the effects of beta-3 drugs with other potential drugs acting at other types of noradrenaline receptors. One of the actions of beta-3 agonists is related to the uptake of glucose into cells in the brain. We will investigate whether the mechanism of beta-3 enhancement of memory involves the uptake of glucose in brain tissue and studies in cultures of individual cell types will show us which cells are involved. Although this work is done using young chicks, there is no reason to suppose that the basic memory mechanisms at the level of the nerve cell should be different in birds or mammals. There are distinct advantages to using chicks in this research as they can form a long lasting memory for an experience lasting only 10 seconds, and they will discriminate between different colours as part of their learning. This research is aimed at understanding the processes involved in and influencing memory formation. If we are going to develop drugs to alleviate the cognitive problems of old age and more serious cognitive diseases, we need to understand more about the basic mechanisms of memory formation in the normal animal.Read moreRead less
Does Exercise Increase Skeletal Muscle Insulin Sensitivity Via Nitric Oxide?
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Almost one in four Australian adults have either diabetes or impaired glucose metabolism. A major benefit of exercise is that it increases the sensitivity of muscle to insulin for many hours after the exercise is completed. We don't fully understand the mechanisms that exercise increases muscle insulin sensitivity. If we discover how nitric oxide production during exercise is involved, drugs that mimic these exercise effects may be designed to benefit those with diabetes.
The Role Of Nitric Oxide In The Regulation Of Skeletal Muscle Glucose Uptake During Exercise
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participa ....When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participate in blood flow, nerve transmission and immune function, appears to be a necessary component for muscle glucose uptake at rest and during exercise. We have shown that blocking muscle NO production substantially reduces leg glucose uptake during exercise. The aim of this project is to verify this finding and to determine the mechanisms underlying this result. One way we intend to do this is to see whether a drug (Viagra) which increases the effects of NO, raises muscle glucose uptake at rest and during exercise. In rats, a drug almost identical to Viagra stimulates muscle glucose uptake. If Viagra is shown to increase glucose uptake this information may provide the initial human data necessary to develop new drugs to lower blood glucose levels in people with diabetes.Read moreRead less
Protecting Synaptic Connectivity In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$573,573.00
Summary
In Alzheimer’s disease, connections between neurons (synapses) are progressively damaged. The BACE inhibitor class of drugs entering Phase III clinical trials may slow the pace of neurodegeneration in patients with dementia. However, these drugs may simultaneously have negative effects on synapse function, learning and memory. This study will assess the effect of BACE inhibition on synapse properties and cognition and identify the contribution of key proteins affected by this treatment.
IRAP inhibitors are currently being developed as a new class of drugs for treating dementia and other forms of memory deficits. However, there are still gaps in our knowledge about how these drugs act to improve memory. The experiments outlined in this proposal will provide important insights into the drug action in different mouse models of memory deficit.
Glucose, Glucose Transporters And Blastocyst Formation In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$281,650.00
Summary
Embryo-based biotechnologies have the potential to improve human reproductive health, notably in treating infertility by In vitro fertilisation (IVF). They are also central to the future use of embryonic stem cells for human tissue replacement. This project investigates the molecular mechanisms controlling one of the earliest differentiations in the growth of the embryo. Using the mouse as an experimental model it will investigate the importance of several factors in the changes which set up the ....Embryo-based biotechnologies have the potential to improve human reproductive health, notably in treating infertility by In vitro fertilisation (IVF). They are also central to the future use of embryonic stem cells for human tissue replacement. This project investigates the molecular mechanisms controlling one of the earliest differentiations in the growth of the embryo. Using the mouse as an experimental model it will investigate the importance of several factors in the changes which set up the placenta and fetus as seperate tissues in the very early embryo. A key focus is the supply of glucose to the newly fertilised embryo and how important this glucose supply is for the survival of the embryo. Moreover there is great interest in the possibility that metabolic events in utero can contribute to the development of diseases in later life, notably, coronary heart diease, stroke, high blood pressure and non-insulin dependent diabetes. The results from these studies will contribute to our understanding of why some couples are infertile, lead to improved management of infertility by diet and invitro fertilisation procedures. It will also be of benefit in dietary advice to women with diabetes mellitus, seeking to have children. The adenoviral strategy for gene delivery into early mouse embryos may in the long term also find wide clinical application in the treatment of genetic defects at the very earliest stages in development and as such is of enormous potential benefit in the management of both animal and human reproduction.Read moreRead less