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.
A Potential Analgesic Target In A Novel Clinically-relevant Neuropathic Pain Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$685,811.00
Summary
Persistent pain arising from tissue damage, to nerves, muscles or joints for example, is devastating for patients and a huge social and economic burden. This work will investigate one of the pathways that goes awry after sensory nerves are damaged. These experiments will also test whether a drug being developed to treat Alzheimer's disease is effective at blocking the persistent nerve hypersensitivity that sometimes develops after injury.
Repurposing An Alzheimer’s Trial Drug To Block Relapse In Cocaine Addiction Models
Funder
National Health and Medical Research Council
Funding Amount
$1,050,601.00
Summary
Repeated exposure to drugs of abuse, such as cocaine, alters the reward circuitry of the brain. Enduring changes in the connections between neurons underlie addiction-related behavioural patterns, drug craving and the propensity for relapse after drug withdrawal. The pre-clinical research in this proposal aims to test whether blocking the function of a particular brain protein in mice can prevent relapse in two different paradigms that model cocaine addiction in humans.
Neuron To Glia Signalling: Learning How Synaptic Signalling Can Promote CNS Remyelination
Funder
National Health and Medical Research Council
Funding Amount
$609,650.00
Summary
An immature cell type in the brain, known as the oligodendrocytes progenitor cell (OPC), receives direct electrical communication from neurons. This communication regulates the behavior of the OPC, affecting its ability to divide and generate new brain cells. This project will identify the signaling molecules that guide the OPC to for this specialized contact with the nerve cell. Understanding this communication has important implications for the treatment of Multiple Sclerosis.
Investigating Secondary Effects Of BACE1 Inhibition, A Promising Therapy For Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$700,672.00
Summary
Synapses transfer information between neurons in the brain. In Alzheimer’s disease (AD), synapse loss results in dementia therefore it is imperative that any potential therapeutic drugs do not inadvertently cause further synapse loss. Drugs aimed at blocking production of toxic protein fragments in AD might have adverse secondary effects on synapse development and function. This research will determine whether this is the case and inform new therapeutic approaches aimed at minimizing side effect ....Synapses transfer information between neurons in the brain. In Alzheimer’s disease (AD), synapse loss results in dementia therefore it is imperative that any potential therapeutic drugs do not inadvertently cause further synapse loss. Drugs aimed at blocking production of toxic protein fragments in AD might have adverse secondary effects on synapse development and function. This research will determine whether this is the case and inform new therapeutic approaches aimed at minimizing side effects.Read moreRead less
Molecular Mechanisms Underlying Recovery From General Anaesthesia
Funder
National Health and Medical Research Council
Funding Amount
$335,983.00
Summary
Even though general anaesthesia is an extremely common and safe procedure, doctors do not really know how it works. We have found that general anaesthetics might work in two steps, by first promoting natural sleep, and then by impairing communication between all nerve cells in the brain. It is this second step that makes surgery possible, but also makes recovery difficult – especially among patients with brain disorders. Understanding these mechanisms will promote better anaesthesia procedures.
The amygdala is a part of the brain that processes and lays down emotional memories. Dysfunction in the amygdala is responsible for anxiety related disorders such post-traumatic stress disorder. I will study the neural circuits in the amygdala using innovative recordings and stimulation techniques. These studies will provide insight into the circuits that underpin anxiety related neurological disorders and provide targets for development of novel anxiolytic agents.
Neurodevelopmental Role Of Susceptibility Genes For Autism Spectrum Disorders: From Genes To Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$482,968.00
Summary
Autism is a developmental neuropsychiatric syndrome characterised by impairments in three principal domains: social interaction, language and behavioural inflexibility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental syndromes with the common feature of dysfunctional reciprocal social interaction. In this project we will investigate the role of genes that increase the risk of ASD in the development of behaviours using an animal model. This work will lead to a better unders ....Autism is a developmental neuropsychiatric syndrome characterised by impairments in three principal domains: social interaction, language and behavioural inflexibility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental syndromes with the common feature of dysfunctional reciprocal social interaction. In this project we will investigate the role of genes that increase the risk of ASD in the development of behaviours using an animal model. This work will lead to a better understanding of the genetic basis of ASD.Read moreRead less
Characterisation Of The Molecular Mechanisms Of Abeta-induced Proteolysis Of The Neural Cell Adhesion Molecule 2 (NCAM2)
Funder
National Health and Medical Research Council
Funding Amount
$374,666.00
Summary
Neurons in the brain are connected by synaptic contacts. Amyloid beta peptide accumulating in the brain in Alzheimer’s disease destroys synaptic contacts by degrading synaptic cell adhesion molecules which maintain the structure of the contacts. The aim of the project is to characterise the molecular mechanisms of amyloid beta-dependent degradation of synaptic cell adhesion molecules. The project will identify strategies that can be used to inhibit synapse loss in Alzheimer’s disease.
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.