Research Theme

Neuroscience

Neuroscience is a scientific discipline that studies the structure, function, development, genetics, biochemistry, physiology, pharmacology and pathology of the nervous system.

Disorders related to the nervous system represent a major and increasing burden on health care. Hundreds of thousands of Australians are affected each year by diseases of the brain and nervous system, such as epilepsy, depression, learning difficulties, stroke, Parkinson's disease, Alzheimer's disease, multiple sclerosis and motor neurone disease. It is estimated that 75% of Australians will suffer some form of nervous system disorder during the course of their life.

Researchers at the Menzies Research Institute aim to increase our understanding of the neuronal systems involved in these disorders and contribute to better ways to prevent and treat them.

Some examples of research projects within the Neuroscience research theme at the Menzies Research Institute:

In vitro study of cellular responses of olfactory ensheathing cells triggered by exposure to bacteria

Olfactory ensheathing cells (OECs) are unique cells in the nose that envelop the nerves involved with the sense of smell. In a recent analysis of the genetics of OECs, we discovered that OECs may have a significant role to play in immune response compared to other supporting cells of the nervous system. This project aims to determine the ways that OECs respond after exposure to certain microbial molecules and bacteria. The results will reveal whether OECs have the capacity to mount a biologically significant response and possibly act as a protective agent in preventing bacterial infection in the nose.

We demonstrated that OECs were attracted to bacteria. Many bacteria that were internalised by OECs were later digested by the cells. In addition, exposure to bacteria caused an increase in the rate of nitric oxide production. Some of these results will be published shortly in Glia. 

Modulation of astrogliosis by olfactory ensheathing cells

Transplantation of OECs has been used to promote repair in the injured central nervous system with varying degrees of success. This project utilises an in vitro model to examine whether or not OECs are able to prevent the negative effects of scarring that develops following injury. The influence of OECs is compared to those other types of cells, such as Schwann cells and microglia.

We demonstrated that in contrast to Schwann cells, OECs were able to reduce the rate of production of chemicals such as glial fibrillary acidic protein (GFAP) and chondroitin sulphate proteoglycan in reactive astrocytes, the major supporting cell within the brain.

At the same time, OECs and Schwann cells were also found to stimulate an increase in the reproduction of astrocytes. Under specific culture conditions, microglia were shown to increase the expression of a particular gene in astrocytes, suggesting that unlike OECs, they may be contributing to increased scarring.

For more information, contact:

Associate Professor Meng Inn Chuah

Senior Member

Telephone: (03) 6226 2664

 

The Laboratory of Molecular Neurobiology

Research in the laboratory is aimed at understanding mechanisms of brain development and ageing. The primary focus of research is to examine molecular mechanisms which control axon pathfinding and synaptogenesis in the normal brain and which contribute to neuritic dystrophy and cognitive dysfunction in diseases such as Alzheimer’s disease. In particular, the group is interested in understanding ageing and Alzheimer’s disease from a developmental perspective.

For more information, contact:

Professor David Small

Senior Member

Telephone: (03) 6226 7348

The Tasmanian Cognition and Gait (TASCOG) Study

TASCOG is studying the effects and mechanisms of age-related brain changes on gait, balance and cognition in a population-based sample of Tasmanian people aged at least 60 years. The study is measuring brain structural changes identified by magnetic resonance imaging (MRI), and examining in detail the effect of the changes on key aspects of brain function. A further aim of the study is to discover factors that can be modified or treated in order to prevent dementia and falls.

This study has progressed rapidly and has exceeded its initial recruitment targets. Of the 400 participants required by December 2007, 360 have already been recruited and measurements have been completed for 285. MRI scans have been analysed for 239 subjects.

Initial analyses have commenced, looking at the effect of brain structure changes on gait and cognition, the effect of age on gait and balance, and the relationship between cognition and gait. These preliminary analyses indicate that brain structure changes are correlated with several gait and balance variables.

For more information, contact:

Associate Professor Leigh Blizzard

Senior Biostatistician

Telephone: (03) 6226 7719

The Ausimmune Study (The Australian Multicentre Study of Environment and Immune Function)

The Menzies Research Institute is continuing to conduct the Tasmanian component of this large Australian Study, with other study regions in Brisbane, Newcastle and Geelong.  Menzies staff are contributing to the overall scientific conduct of the study and related studies, such as an investigation of whether people with early demyelinating disease have a higher viral load of viruses such as Epstein-Barr Virus and Human Herpes Virus 6 in their blood at first presentation compared to age matched controls. The Tasmanian region has had good participation rates compared to some other regions.

Longitudinal Cohort Study of Multiple Sclerosis in Southern Tasmania

The cohort has had serial clinical reviews at six-monthly intervals. The final cycle of data collection was completed in February 2005. Researchers are focussing on environmental determinants of disease progression, for the purpose of developing new interventions to slow MS progression. Further funding was obtained to allow genetic assessment of disease progression, with a special emphasis on immunogenetics. Magnetic resonance imaging scans have been assessed in collaboration with St Vincent’s Hospital, Melbourne.

The Tasmanian Environmental Control Study of MS

This case control study has been very informative to date and this was recognised by NHMRC in a report on the most productive NHMRC grants funded from 1999-2003. The study has particularly provided information on the possible role of early life factors such as low sun exposure, low contact with infants and infection in determining the risk of Multiple Sclerosis. The study team is working with the Genetics group to explore gene-environment interactions in MS.

Click here to download the latest brochure on Information on Vitamin D levels for People with MS. 

Does binocular vision training enhance literacy among children with low literacy?

Past work has shown that some children with normal intelligence have reading problems because of problems coordinating both eyes to read visual images. The Literacy Pathways project screened for vision coordination problems among children with low literacy. Children who were found to have problems with their binocular vision were invited to participate in an educational trial designed to improve their reading.

The vision screening of eligible children was completed in 2006. The study design for the randomised control trial was finalised and the Project Officers completed their training for the interventions. One hundred and twenty one children were eligible for the ten week trial and 89 children agreed to participate. Seventy-nine children completed the post-assessments. Data analysis and the six month follow-up will be conducted in 2007.

Visit the Literacy Pathways page on the Institute for Inclusive Learning Communities website.

For more information, contact:

Associate Professor Anne-Louise Ponsonby

Senior Member

Telephone: (03) 6226 7700

The Tasmanian Parkinson’s Disease Research Project

The Tasmanian Parkinson's Disease Research Project is examining the genes that cause Parkinson's disease and aims to discover other genes that have not been linked to the disease before. Identifying inherited risk factors will provide a better understanding of the way that Parkinson's disease develops and is an important step towards preventing and treating the disease.

Previously we have focussed on an investigation of the genetic causes of Parkinson’s disease in people with a strong family history of the condition. In 2006, we expanded our search for the genetic causes of Parkinson’s disease in a much larger sample of Tasmanians. With the help of Medicare Australia, 996 Tasmanians were identified as receiving medication commonly prescribed for Parkinson’s disease; all were invited to participate in the study. Three hundred and thirty-five eligible people agreed to participate by completing a questionnaire and providing a saliva sample from which DNA was extracted.

For more information, contact:

Associate Professor Alison Venn

Deputy Director

Telephone: (03) 6226 7706

Nerve Cell Plasticity and the Neuropathology of Parkinson’s disease

Parkinson's Disease (PD) is one of the most common neurodegenerative disorders. Its incidence increases steadily with age affecting approximately one per cent of the population at age 65 and up to five per cent by the age of 85. At the time of diagnosis, patients suffer from a range of motor impairments that worsen over time. Pathologically these patients are characterised by the accumulation of a protein known as alpha-synuclein in specific types of nerve cells in their brain. However, the function of this protein is unknown.

This research aims to clarify the role of alpha-synuclein in PD and normal function of the central nervous system and provide new potential therapeutic targets for the treatment of PD and other neurodegenerative disorders in which oxidative stress, excitotoxicity and central nervous system trauma have been implicated.

Our studies found that the protein alpha-synuclein is upregulated in neurones in response to chronic oxidative stress and is associated with neuroprotection. The manuscript describing this result was received by the scientific community with great enthusiasm and interest and as such was selected by the Editors of ‘Experimental Neurology’ as a feature article and was printed with an accompanying invited commentary. This preliminary data contributed to our successful National Health and Medical Research Council Project Grant application which will allow for significant expansion of this project over the next three years.

Cellular Degeneration in Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disease that progresses over the course of many years and has several pathological hallmarks, namely, b-amyloid plaques, neurofibrillary tangles and neuropil threads.  Although much is now known about AD there is still considerable controversy over which of the pathological hallmarks causes the disease, why only certain populations of nerves cells die and how these nerve cells die in AD. The aim of this project is to study the pathological hallmarks of AD in human brains and to utilise in vivo and in vitro models to investigate the crucial cellular changes underlying neurodegeneration in this condition.

The Cause of Neural Degeneration in Motor Neuron Disease

Motor neuron disease involves the selective degeneration of the nerve cells involved in movement in the spinal cord and the cortex of the brain. The reasons for this selective degeneration and the cellular alterations resulting in nerve degeneration are unknown. This aim of this project is to investigate the mechanisms involved in neurodegeneration in motor neuron disease and other neurodegenerative diseases with the ultimate goal of reducing or preventing nerve cell death. This project utilises novel cell culture methods to model important aspects of the pathology of this condition.

Axon Regeneration in the mature Central Nervous System

Brain and spinal cord injury are major causes of death and disability. The aim of this project is to determine how nerve cells in the brain respond to injury. We have found that the way in which a mature nerve cell attempts regenerative sprouting appears to be very different to the pattern of axonal growth that characterises early brain development. Our research is aimed at determining the cellular features that characterise the adaptive response of nerve axons to damage in the adult brain and comparing and contrasting these with developmental events. It may then be possible to manipulate this axonal response to injury to help damaged brains to repair themselves.

For more information, contact:

Professor James Vickers

Deputy Director

Telephone: (03) 6226 4830

Developing metallothioneins as a therapeutic agent for promoting neuronal recovery from central nervous system injury or neurodegenerative disease

Dysfunction of the central nervous system (CNS) as a consequence of injury or disease has a significant impact upon the entire community.  Unfortunately there are no clinical therapies currently available to either protect neurons from dying or promote neuronal recovery following CNS injury or disease.  However, our recent research has identified the exciting potential of metallothionein (MT) proteins as a neuroprotective and neuroregenerative agent. In this project, we will evaluate the therapeutic potential of MT proteins in several animal models of neuronal injury and neurodegenerative disease, including traumatic brain injury, motor neurone disease and Alzheimer’s disease.

We have commenced animal trials to test the efficacy of MT-based treatments for delaying the progression of neurodegeneration in animal models of motor neurone disease and Alzheimer’s disease. While these trials are still ongoing, the results to date are very encouraging. We are also currently investigating different routes of administration for metallothionein, to determine an optimal method for treatment.

Using metallothioneins as a model for understanding cellular and biochemical interactions between neurons and astrocytes within the brain

We have recently identified a novel and major neuroprotective mechanism within the injured brain, involving an interaction between injured neurons and the major supporting cell wtrhin the brain, astrocytes. This involves the up-regulation and secretion of the astrocytic protein metallothionein (MT), which is then able to directly interact with neurons to promote recovery.

We propose to use this system as a model to enhance our fundamental understanding of some of the cellular and biochemical mechanisms involved in brain function. This research may also provide insight into ways of improved healthy aging.

We have been able to measure the level of secretion of MT from astrocytes, and have identified that the astrocytes must be induced in a certain way to promote secretion of the protein. We have also identified a potential biochemical pathway that regulates the interaction of MT with neurons, and we are investigating this in further experiments.

For more information, contact:

Associate Professor Adrian West

Senior Member

Telephone: (03) 6226 2595

Tasmanian Epilepsy Register study

This study aims to investigate the health of Tasmanians with epilepsy and discover factors that may explain the causes or consequences of having this common neurological condition.

For more information, contact:

Dr Wendyl D'Souza

Research Fellow

Telephone: (03) 9288 3341