The Missing Link: MGluR5 As A Therapeutic Target For Cognitive Decline In Dementia
Funder
National Health and Medical Research Council
Funding Amount
$563,622.00
Summary
Cognitive decline is a core feature of Alzheimer’s Disease (AD), yet there is no cure or treatment. Recent evidence suggests that a protein called mGluR5 could cause brain cells to lose function, leading to memory loss. This project will investigate whether disrupting mGluR5 function can improve cognition in mice with genetic AD. Memory will be assessed in mice using innovative touchscreen tests that closely mimic the tests used in humans.
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.
Brain Connectivity Biomarkers Predict Specific Memory Consolidation Deficits Across Dementia Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$83,149.00
Summary
With the increasing ageing population there is expected to be a significant increase in the number of dementia cases in the near future. This project aims to improve the accuracy of existing diagnostic protocols for dementia by combining recent advances in magnetic resonance imaging with traditional cognitive assessments. We expect the outcome to improve detection in the early stages of disease onset so that patients may receive immediate medical treatment.
REVERSIBLE AND IRREVERSIBLE TNF-MEDIATED COGNITIVE DECLINE
Funder
National Health and Medical Research Council
Funding Amount
$444,460.00
Summary
This proposal seeks to clarify the neuronal mechanisms underlying the inflammatory processing leading to cognitive decline. Furthermore, the research project identifies anti-inflammatory treatment options aiming at improved cognitive performance in people at risk for or suffering from cognitive impairment of neuropsychiatric disorders such as dementia and depression.
Site-specific Tau Phosphorylation To Treat And Understand Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$943,902.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia. Unfortunately, current therapies are ineffective. Our laboratory has made an important contribution to understanding the events that lead to brain cell malfunction in AD. I recently found a novel concept that changes the view of AD completely. In the next 3 years, I aim to develop therapeutic tools based on this novel concept and find out more about how it can protect brains from AD.
Ecstasy, Methamphetamine And Their Combination: Assessment Of Adverse Effects
Funder
National Health and Medical Research Council
Funding Amount
$384,250.00
Summary
MDMA (Ecstasy) and Methamphetamine (METH) are popular party drugs that are frequently used by young Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to psychological problems such as anxiety, depression, increased impulsive behaviour a ....MDMA (Ecstasy) and Methamphetamine (METH) are popular party drugs that are frequently used by young Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to psychological problems such as anxiety, depression, increased impulsive behaviour and memory impairment. However the link between MDMA and METH use and subsequent brain damage is still very controversial. Recently, we have found that when MDMA and METH are combined, a particularly toxic effect is seen with very high body temperatures and lasting adverse effects on mood and brain function. This is a major cause for concern because of evidence that many Australian drug users are combining METH and MDMA on a regular basis. This project will investigate the short and long-term effects of MDMA, METH and METH-MDMA combinations. Phase 1 is aimed at investigating whether different doses of the drugs lead to lasting changes in mood, behaviour and brain function and to compare the relative toxicity of the three treatments. Phase 2 will determine whether lack of fluid intake, high environmental temperatures and advanced age are risk factors in determining the toxicity of MDMA and METH. Phase 3 will assess whether the toxicity of these drug treatments depends upon whether an animal takes the drugs voluntarily or whether they are injected with the drug by the experimenter. The final part of the project will use a wide variety of advanced techniques to track the brain damage caused by these drug treatments given under a range of conditions. The significance of this project will be in increasing our understanding of how MDMA and METH affect the brain and behaviour and how the harms posed by these drugs may be predicted and therefore minimised.Read moreRead less
How are memories stored in the brain? We know much about the brain regions involved in memory storage but we know little or nothing about how individual memories are represented and stored within those brain areas. The purpose of this project is to label and manipulate the specific subsets of brain cells that store individual memories. We will label memory-bearing cells in multiple brain regions and then ask how the connections between those cells encode learned information in the brain.
Humans, like all animals, receive similar, although not identical, visual input via the eyes. This information is combined in the brain to form a single view of the outside world. In this proposal we aim to understand how single neurons in the brain process the combined information received from both eyes. This work will increase our understanding of the underlying cellular mechanisms responsible for sight, and determine what changes occur when visual input is impaired through blindness.
Microglia As Primary Drivers Of Stress-induced Changes In Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$475,781.00
Summary
Persistent exposure to stressful events can produce serious and lasting disturbances in cognitive function. Our research group has recently identified that microglia may play a very significant role in these disturbances. The studies to be undertaken in this proposal will provide fundamental knowledge on how microglia contribute to neuronal plasticity, and how microglia via their effects on neurons regulate complex cognitive behaviour.
Enzymes that generate or degrade peptides serve important roles - alterations in their activity can impact on a diverse range of physiological processes in healthy and diseased states. Angiotensin is a peptide that plays a critical role in regulating blood pressure and fluid balance - drugs that block the activity of its processing enzymes forms an important class of medication used to treat hypertension and heart disease. My research interest is in discovering novel roles for these enzymes.