Previous Grants

The following grants were approved by the Neurological Foundation National Council:

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> Millennium Post-Graduate Scholar
> Philip Wrightson Postdoctoral Fellowship
> W & B Miller Post Graduate Scholarships
> Sarah Lowes Travel Awards
> VJ Chapman Research Fellowship
> Summer Studentships

>> Research Project Grants

The Neurological Foundation of New Zealand Human Brain Bank - 2007		$ 260,505 (over three years)
	Prof Richard Faull Department of Anatomy with Radiology,University of Auckland In 1993 we established the Neurological Foundation of New Zealand Human Brain Bank to provide for the collection of human brain tissue to facilitate and promote research studies on the major neurodegenerative diseases of the human brain (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, epilepsy, schizophrenia). The Brain Bank is now well established and is internationally recognised as a unique resource of high quality tissue for research studies in New Zealand and overseas.

Can brain stimulation reverse cognitive/emotional effects of vestibular lesions? - 2007		$ 117,279
	Prof Neil McNaughton, Prof Paul Smith, Associate Prof Cynthia Darlington Departments of Psychology and Pharmacology,University of Otago Disruption of brain “theta” activity affects learning, memory and anxiety-related behaviours in animals. Vestibular damage disrupts theta activity in rats and produces cognitive and emotional deficits in humans. We have recently shown that electrical stimulation via a “brain bypass” can restore theta activity and cognitive function in rats. We will determine whether this is also effective with vestibular-lesioned rats; and whether a simpler fixed-frequency stimulation method is similarly effective. Our goal is to determine whether deep brain stimulation, eliciting theta rhythmicity, could improve cognition and emotion in patients with vestibular damage and, subject to further tests, disorders such as dementia.

Controlling acetylcholine in the brain - a therapeutic target for Parkinson's disease? - 2007		$ 171,789
	Dr Manfred Oswald, Dr John Reynolds Department of Anatomy and Structural Biology,University of Otago Medical School Our aim is to identify new ways to control acetylcholine release, which may present new targets for therapeutic intervention in Parkinson’s disease. In Parkinson’s disease there is an excessive amount of acetylcholine which until now has been thought to be directly related to the loss of another neurochemical dopamine. We believe that dopamine loss is not the direct cause, but instead another system which normally keeps acetylcholine levels under control plays a major role. We will use state-of-the-art recording methods to determine how this system, involving cells in the cortex and thalamus, controls the activity of the cholinergic cells.

Use of in vivo microdialysis to measure neurochemical consequences of MDMA selfadministration - 2007		$ 96,127
	Prof Susan Schenk School of Psychology,Victoria University of Wellington Drug abuse has reached epidemic proportions in New Zealand and around the world. The consequences of compulsive drug abuse on brain structure and function, however, are not well understood. A number of studies have suggested that compulsive use of drugs compromises brain systems that use the neurochemicals dopamine and serotonin. In order to assess this possibility, this project aims to measure these brain chemicals in rats that have self-administered MDMA (“ecstasy”) in order to determine changes that might underlie the long-term effects and compulsive use of this drug.

Mean-field modelling of anaesthesia and seizures: testing model predictions in rat cortical slices - 2007		$ 92,800
	Prof. James Sleigh, Dr Logan Voss University of Auckland, Waikato Clinical School, University of Waikato, Hamilton Using a mathematical model of brain (cortex) function, we have addressed the paradoxical question: “How do general anaesthetic drugs - which act to depress neuronal firing - cause seizures in some cases?” The aim is to validate the accuracy of the computer-based model by investigating seizure induction in real animals. If proven to be accurate, the model could increase our understanding of seizures/epilepsy, and brain cortex function in general anaesthetic mechanisms-of-action. It could also provide a rationale for the use of combinations of different classes of drugs to be used to treat seizures/epilepsy.

Are dorsal raphe neurons activated by reward prediction? - 2007		$ 139,903
	Assoc. Prof. Brian Hyland Department of Physiology,University of Otago Patients with Parkinson’s disease, predominantly a disorder of movement, can suffer from depression, whereas patients with severe depression sometimes show slowed movements reminiscent of Parkinson’s disease. These crossover symptoms might reflect interaction of different chemical systems in the brain that are involved in regulating movement and mood. This project will investigate, in an animal model, whether the 5-HT, or serotonin, system, a target for drugs treating depression, might play a role in controlling the dopamine system, the chemical pathway that degenerates in Parkinson’s disease. The results may shed light on why these seemingly disparate diseases can share some symptoms.

Directing Adult Neurogenesis and Cell Migration for Brain Repair - 2007		$ 126,094
	Dr Bronwen Connor, Dr Ailsa McGregor Department of Pharmacology and Clinical Pharmacology,University of Auckland Neural progenitor cells found in the adult brain may provide an exciting therapeutic strategy for replacing cells lost through brain injury or disease. In order to achieve this clinically, methods must be developed to direct progenitor cells to migrate to specific areas of cell loss. One signalling system that may be of importance in this regard is the chemokines and their receptors. This project therefore aims to advance our knowledge regarding the role of chemokines in the adult brain and identify the potential for specific chemokines to direct the migration of neural progenitor cells to areas of brain injury and disease.

Does a calcium channel gene on the X-chromosome confer susceptibility to autism? - 2007		$ 66,068
	Dr Marion Maw Department of Biochemistry,Department of Biochemistry, University of Otago Autism is a behaviourally defined disorder that arises from abnormal development of the brain. Twin studies suggest that affected children have inherited an unfortunate combination of multiple genetic factors, each of which may only moderately increase the risk of developing autism. A New Zealand family is affected by an inherited condition that is associated with intellectual impairment and autism. We have shown that this rare disorder is caused by a mutation in a calcium channel gene. In the present study, we will investigate whether mild variants in this same gene are a risk factor for autism in the general population

Saccadic function in Alzheimers disease: an fMRI study - 2007		$ 68,166
	Prof. Tim Anderson, Assoc. Prof John Dalrymple-Alford, Dr Michael MacAskill, Dr Richard Watts, Professor Tim . Wilkinson, Mrs Saskia Van Stockum, Dr Ross Keenan Christchurch School of Medicine and Health Sciences,University of Otago Dementia is increasing world wide and about 8% of people over 65 years are affected, with numbers expected to triple in the next 50 years. Much effort and money is being spent on finding an effective treatment though none has been forthcoming as yet. The aim of this research project is to look for abnormalities of fast eye movements (saccades) in people with Alzheimer’s disease, the commonest dementia, and to simultaneously map brain function using New Zealand’s only 3 Tesla MRI scanner. This should tell us just which areas in the brains of people with Alzheimer’s are not functioning properly when glancing at objects of interest. We hope to eventually use this information to follow or even predict the progress of people’s Alzheimer’s, and especially as a way to monitor response to new therapies when they become available

Synaptic targets for brain repair - 2007		$ 80,000
	Dr Johanna M Montgomery, Dr Bronwen J Connor, A/P William N Green, Dr David Genoux Department of Physiology,University of Auckland Neurodegenerative disease induces massive brain cell loss which we cannot repair. The ability for the adult brain to produce newborn neurons represents a powerful potential treatment for these diseases but only if we acquire a complete understanding of how newborn neurons integrate into the brain. We aim to visualise the functional integration of newborn neurons and determine how a specific family of synaptic proteins control this process. Because these proteins are critical regulators of synapse function, we aim to identify whether these proteins are significant effectors of regeneration of the brain.

Metabotropic Glutamate Receptor Signalling in Cerebellar Ataxia - 2007		$ 180,284
	Dr Ruth Empson Department of Physiology,University of Otago When did you last take for granted your ability to enjoy a cup of coffee without spilling it everywhere? Ataxia, or loss of controlled movement, occurs when the electrical circuits in a part of your brain called the cerebellum start to go wrong. It can affect anyone, young or old, has a variety of causes, usually gets worse and is rarely reversible. In this project we aim to better understand how the electrical circuits within the cerebellum start to go wrong in ataxia. With this information we aim to design approaches to rescue the defective circuits.

Novel neuroprotective strategy against ischemia/reperfusion injury based on co-application of mitochondria-targeted antioxidants and TRMP2 channel blockers - 2007		$ 57,452
	Prof. Janusz Lipski, Dr. Michael Grammer Department of Physiology,University of Auckland Years of research indicate oxidative stress has a significant role in brain damage associated with stroke, and yet, almost all clinical trials have found antioxidant therapy to be ineffective. In this study, we propose a novel approach to protect the brain from oxidative stress during stroke using newly developed ‘smart’ antioxidants which specifically target the mitochondria, where oxidative molecules are produced. To further increase the effectiveness of these antioxidants, we also propose to simultaneously block a cell membrane channel (TRPM2) recently identified in oxidant-induced cell death processes. We hypothesize that such a combined approach will significantly advance the treatment of neural damage caused by stroke and other neurological disorders associated with similar cell death mechanisms

Early prediction of brain damage after acute brain injury in children - 2006		$ 75,755
	Dr John S Beca, Assoc Prof Chris E Williams, Assoc Prof Brian J Anderson, Dr Melinda A Nolan, Dr Claire G Spooner Paediatric Intensive Care Unit,Starship Children's Health, Auckland District Health Board Injury to the brain is the commonest cause of death and disability in children and exceeds all other causes combined. When the brain is injured damage may continue to occur for days, providing a window of opportunity for treatment. However we lack the ability to monitor the brain to determine how severely it has been damaged and whether ongoing damage is occurring. The purpose of this project is to investigate whether advanced monitoring can achieve these things. The monitors include an electrical monitor developed in New Zealand, a monitor of brain oxygen levels and advanced brain scans.

Interleukin-4 receptor: a regulator of susceptibility to multiple sclerosis - 2006		$ 177,014
	Dr. Anne C. La Flamme, Dr. Diane Kenwright, Dr. Paula Keating Victoria University of Wellington The debilitating neurological disease, multiple sclerosis (MS), is characterized by immunemediated nerve degeneration. Although T cells are responsible for the immune targeting of nerves, macrophages also play an essential role in disease by allowing entrance of inflammatory cells into the central nervous system. We have found that the macrophage’s ability to respond to the protein, interleukin (IL)-4, controls development of MS. This proposal will determine the pathway by which IL-4 alters macrophage function and regulates disease progression. Identification of disease-inhibiting and promoting pathways may uncover new therapeutic targets for clinical inhibition or reduction in the severity of MS.

Neuroprotective potential of antibiotics in models of stroke - 2006		$ 118,241
	Prof. Janusz J. Lipski Department of Physiology,University of Auckland Stroke is a sudden failure of part of the brain which results from the interruption of the blood supply to that area. It is the third most common cause of death, and the main cause of long-term disability in New Zealand. Damage of nerve cells in stroke is largely due to the excessive release of a chemical known as glutamate. Using established in vitro models of stroke, we will investigate the exciting new concept that damage to nerve cells can be reduced by a group of antibiotics known as ?-lactams. Ceftriaxone and other antibiotics belonging to this group have recently been shown to enhance the expression of glutamate-mopping up molecules known as glutamate transporters. Our project will explore the potential of ceftriaxone for enhancing glutamate transporter expression in a highly vulnerable part of the brain known as the hippocampus, and for neuroprotection against nerve cell damage resulting from simulating the conditions of stroke. This study should contribute to the development of novel stroke therapies based on the use of ?-lactams. The ultimate goal is to reduce deaths from stroke and lessen the devastating effects on survivors

Development of the Borderdale sheep model of CLN5 Batten disease - 2006		$ 123,522
	Dr David N Palmer, Dr Graham W Kay Lincoln University Batten disease is a group of devastating neurodegenerative diseases of children. Much has been learnt about it from studying affected animals. The development of a flock of sheep with a form caused by a soluble enzyme defect provides an exciting model to explore aspects of the disease leading towards treatment. Early inflammation in the brain will be studied, to determine if anti-inflammatory drug therapy is likely to be of benefit, as well as the continued formation of new nerve cells from precursor cells in a particular area of the brain that may provide a target for gene therapy.

SIRT1: a link between environment and improved cerebral health? - 2006		$ 100,000
	Dr Deborah Young Department of Molecular Medicine & Pathology,University of Auckland One method for promoting healthy brain ageing and reducing the risk for development of age-related memory decline is to regularly engage in stimulating intellectual activity, cut back on the calories and ensure that exercise is incorporated as part of a regular routine. This project aims to understand how these behavioural interventions can positively influence brain function and increase resistance to genetic or environmental stressors. We propose that SIRT1, a protein that can control several protein regulators of cell death and survival is a key link between environment and improved cerebral health.

Effects of CX516 on cognitive deficits following vestibular damage - 2006		$ 92,177
	Dr Yiwen Zheng, Prof Paul F Smith, Assoc Prof Cynthia L Darlington Department of Pharmacology and Toxicology,University of Otago People with damage to the balance organs of the inner ear experience dizziness, but also suffer from memory problems related to shrinkage of a brain region called the hippocampus. We aim to test a new drug treatment to prevent or reverse the effects of the inner ear damage on the hippocampus. The effect of a chemical called glutamate is reduced in the hippocampus after inner ear damage. Therefore, we propose to determine whether a drug (an ampakine) that increases the effect of glutamate in this part of the brain prevents or reverses the damage to the hippocampus and memory impairment.

Agmatine and age-associated cognitive decline - 2006		$ 155,209
	Dr Ping Liu Department of Anatomical and structural biology,University of Otago We tend to learn slowly and forget quickly when we are old. Elevated level of an endogenous gas named nitric oxide (NO) has been shown to contribute to such age-related cognitive decline. Agmatine is a neurotransmitter and an endogenous regulator to control NO production. Our preliminary work has demonstrated a decreased agmatine level in the aged brain, which may account for increased NO production and poorer learning and memory ability during aging. This project will further test this possibility using multiple techniques.This work may lead to a future therapeutic intervention for cognitive impairments in normal aging and Alzheimer’s disease.

Finding the substrate upon which deep brain stimulation acts to relieve parkinsonian symptoms. - 2006		$ 142,843
	Professor Gordon W Arbuthnott, Assoc. Prof Brian I Hyland, Professor Jeffery R Wickens Depts of Physiology and Anatomy and Structural Biology,University of Otago Drug treatment for Parkinson’s disease works well initially, but becomes less effective as the disease progresses. Internationally, such patients are increasingly treated by deep brain stimulation, which involves inserting electrodes into the brain and applying continuous electrical stimulation to a structure deep in the brain. While effective, the mode of action of this invasive surgical procedure is not understood. This project aims to discover the mode of action of the stimulation in the hope of developing less invasive methods, which might have an equivalent efficacy.