Allosteric Targeting Of The Dopamine D2 Receptor: A Novel Approach For The Treatment Of Parkinson’s Disease And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$469,644.00
Summary
The dopamine D2 receptor is a brain protein that is the target for drugs that are used in the treatment of schizophrenia and Parkinson's disease (PD). In both cases the current drugs have significant side effects because they simply act to switch the receptor off or on respectively. We will focus on a new class of drugs that, because they act to tune up or tune down the activity of the D2 receptor, may be a safer more effective approach to treat these disorders.
A New Animal Model Of The Prodrome In Schizophrenia. Enhanced Dopamine In Prodromal Schizophrenia (EDiPs)
Funder
National Health and Medical Research Council
Funding Amount
$571,990.00
Summary
Psychiatrists now recognize a pre-symptomatic stage is present in people at risk of developing schizophrenia. Using new brain imaging techniques we now know that some of these individuals have changes in a major neurotransmitter, dopamine, prior to being diagnosed. We have developed a new model in animals, which recreates these exact same changes at a comparable age. We want to now understand what are the broader effects in the brain and try and block these changes in dopamine with new drugs.
Mephedrone (Meow, 4-Methylmethcathinone): Examining The Effects Of A Novel Party Drug On Brain And Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$399,796.00
Summary
Mephedrone ("Meow") is a novel recreational drug that has rapidly increased in popularity in recent years. Users report that mephedrone has the stimulant-like qualities of cocaine, combined with the prosocial effects of MDMA. Anecdotal and case study reports indicate that mephedrone may have the potential to engender compulsive patterns of use as well as toxicity in overdose. The current project will use animal models to assess how mephedrone affects the brain and behaviour and to assess its add ....Mephedrone ("Meow") is a novel recreational drug that has rapidly increased in popularity in recent years. Users report that mephedrone has the stimulant-like qualities of cocaine, combined with the prosocial effects of MDMA. Anecdotal and case study reports indicate that mephedrone may have the potential to engender compulsive patterns of use as well as toxicity in overdose. The current project will use animal models to assess how mephedrone affects the brain and behaviour and to assess its addictive potential.Read moreRead less
Dopamine Neuron Ontogeny: Convergent Neurobiological Pathway For Risk Factors Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$337,214.00
Summary
Schizophrenia is associated with changes in dopamine (a signalling molecule in the brain). These changes are present prior to psychosis, suggesting they begin early in development. Our aims are to manipulate key factors in the development of brain dopamine systems to clarify their role in psychosis and schizophrenia. This work has the potential to identify early brain changes that lead to schizophrenia, which in turn may generate better diagnoses and outcomes for people with this disorder.
Developmental Vitamin D Deficiency And Prefrontal Cortical Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$355,570.00
Summary
The cause of schizophrenia is unknown but is believed to be due to abnormal brain development. Dopamine abnormalities are central to schizophrenia. We have developed a model of maternal vitamin D deficiency in rats, based on disease epidemiology that shows individuals that have low levels of vitamin D at birth have an increased risk of developing schizophrenia later in life. We now also show dopamine systems in regions associated with cognition may develop abnormally in our animal model.
The Role Of Meninges In Midbrain Dopamine Development
Funder
National Health and Medical Research Council
Funding Amount
$378,311.00
Summary
Dopamine neurons are important for the control of movement, emotion and cognitive function, and are affected in a number of disorders such as Parkinson’s disease. Instrumental in improving our knowledge of disease etiology and the development of new therapies will be a greater understanding of how these cells are initially born during development. This project examines the role of the brain’s meninges in dopamine development and repair and will identify proteins and signaling pathways involved.
Testing The Prion Hypothesis In Parkinson’s Disease Using A Novel In Vivo Model Of Α-synuclein Transmission
Funder
National Health and Medical Research Council
Funding Amount
$622,555.00
Summary
Parkinson’s Disease (PD) is a debilitating neurological disease with no cure. Recently it has been discovered that the disease can spread through the brain. We have developed the worlds first animal model to study exactly how the disease propagates inside of neurons during this spread. We will use the model to answer key questions about this critical stage of disease spread, knowledge that is essential for the development of successful therapies to prevent disease progression.
Toward Cell-replacement Therapy For Parkinson's Disease: Investigating Endogenous Dopamine Neurogenesis In The Adult Mouse Substantia Nigra
Funder
National Health and Medical Research Council
Funding Amount
$577,957.00
Summary
Death of a particular type of cell in the brain causes the movement symptoms of Parkinson's disease (PD) (e.g. tremor). This study investigates how these cells are normally replaced, and whether stimulating their replacement can alleviate movement symptoms in an animal model of PD. Fulfillment of these aims will deliver vital information about how we might delay and better treat the movement symptoms of PD.
Human Tyrosine Hydroxylase Isoforms And Susceptibility Of Dopaminergic Neurons To Degeneration In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$359,683.00
Summary
In Parkinson's disease there is major loss of the dopaminergic neurons of the substantia nigra. We are investigating how the control of dopamine synthesis may affect the differential loss of dopaminergic neurons in Parkinson's disease. Understanding why certain dopaminergic die in Parkinson's disease and others do not will help the development of new treatment strategies for Parkinson's disease.
Standardising Protocols For The Differentiation And Integration Of Human Pluripotent Stem Cell-derived Neural Transplants In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$987,664.00
Summary
Clinical trials have shown that transplanting dopamine neurons (specific nerve cells) into the brain of Parkinson’s disease patients can improve symptoms. Trials use fetal tissue for implantation, which is unsustainable and highly variable. This proposal will examine stem cells as an alternative. We will establish a reliable protocol to instruct human stem cells to become dopamine neurons, develop methods to select these cells and, examine the integration of these transplanted cells in the brain