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Scientists receive funding boost to further research into mechanisms of Alzheimer’s disease

Press release issued: 29 July 2011

Neuroscientists at the University of Bristol have received a major funding boost of £550,000 from the Medical Research Council (MRC) to continue their research into the pathological processes underpinning Alzheimer’s disease, the most common cause of dementia, affecting around 465,000 people in the UK.

Neuroscientists at the University of Bristol have received a major funding boost of £550,000 from the Medical Research Council (MRC) to continue their research into the pathological processes underpinning Alzheimer’s disease, the most common cause of dementia, affecting around 465,000 people in the UK.

The funding will be used to continue the team’s latest research into how aspects of electrical signalling go wrong in the Alzheimer’s disease brain. Their initial findings, which formed the basis of the application to the MRC, were published in the journal Neurobiology of Aging. The group is led by Professor Andy Randall and Dr Jon Brown at the University’s School of Physiology and Pharmacology.

Like a computer the brain largely uses electrical signals to encode and convey information. In diseases of the nervous system this electrical signalling becomes disturbed in various ways such that information processing becomes altered and processes like memory are compromised.

The study has utilised a rodent model engineered to exhibit aspects of Alzheimer’s disease pathology in the brain.  By making recordings from single brain cells in the hippocampus (a brain area crucially involved in memory) the researchers have been investigating what is known as “neuronal excitability”. This is a descriptor of how easy it is to produce a brief, but very large, electrical signal called an action potential. Action potentials occur in practically all neurones and are essential for communication within all circuits of the nervous system. They are triggered near the cell body and once produced rapidly travel through the massively branching structure of the neurone, along the way activating the synapses the neurone makes with the numerous other neurones to which it is connected.

The researchers have found that the neuronal excitability is substantially altered in the model of Alzheimer’s disease compared to normal controls. For example, the patterns of action potential produced for any given stimulus are altered. The team also found that in the Alzheimer’s model the action potential shape is changed such that is rises more slowly and is both shorter and narrower. They followed this up by showing the functional levels of an important protein (the voltage-gated sodium channel) that are crucial to producing action potentials are substantially reduced.

These findings are significant as they have identified changes to the generation and waveform of action potentials in a model of Alzheimer’s disease. Given the fundamental role of action potentials in the function of all brain circuits, these changes are potentially very important contributors to the deficits in brain function exhibited by those afflicted with Alzheimer’s disease.     

Professor Randall, Professor in Applied Neurophysiology, said: “As neurophysiologists we directly measure these electrical events in brain tissue and try to understand how they become disturbed by various pathological processes that contribute to diseases of the nervous system. Although many laboratories around the globe have considered this question, the vast majority, including colleagues in Bristol, have concentrated their efforts on understanding altered electrical signalling at synapses, the sites of contact between neurones at which cell-to-cell communication occurs. Although changes at synapses are no doubt important, our alternative approach has identified additional novel disturbances in electrical signalling in the brain which we believe are potentially as significant.”

The research, entitled ‘Altered intrinsic neuronal excitability and reduced Na+ currents in a mouse model of Alzheimer’s disease by Jon T Brown, Jeannie Chin, Steven C.Leiser, Menelas N Pangalos and Andrew D Randall, is published in the journal Neurobiology of Aging.

The research was funded by the University of Bristol and an alliance with Pfizer whose scientists also contributed experimental work to the project.

 

 

Further information

MRC

For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest-quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century.

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