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Fatal brain disease holds clues to dementia

28.04.2005


Scientists at Melbourne’s Howard Florey Institute have uncovered a clue about the causes of dementia in Huntington’s disease, one of the disease’s symptoms, by showing that mice susceptible to Huntington’s disease have problems with learning and memory before the diseases’ typical movement problems appear.



The Florey scientists also discovered that in Huntington’s diseased brains, information processing between neurons is disrupted, but the neurons do not die, which means the brain may respond to new anti-dementia drugs that can restore memory.

Huntington’s disease is an incurable, inherited disorder of the nervous system that affects specific brain regions and inevitably leads to death. Symptoms range from disrupted control of movements and thought processes, and emotional problems. These include: jerky arm or leg movements; difficulties with speech, swallowing, concentration, memory and learning; and depression and personality changes.


Huntington’s disease is caused by a mutation in a single gene. When this defective gene is passed from parent to child, 50 percent of the offspring will inherit the disorder, which can be detected by genetic testing.

Research leader Dr Anthony Hannan said his team’s investigations were significant as they could lead to the development of memory restoring drugs designed especially for people with Huntington’s disease.

"We have demonstrated the linkage from molecule to cell to learning and memory, and can relate this to a particular area of the brain," Dr Hannan said.

"Our work shows that the defective huntingtin gene disrupts how large groups of neurons ’talk’ to one another and adjust their wiring in response to stimulation from the environment."

"Now we can better understand how a genetic change affects wiring of neurons and relate that to changes in learning, memory and behaviour in Huntington’s disease."

"By better understanding the disease mechanism, we can work towards developing drugs to treat dementia in people with Huntington’s disease," he added.

Dr Hannan’s team trained normal and Huntington’s disease-susceptible mice to perform a complex touch-dependent learning task. The healthy mice could improve on their performance and learn the task, but the mice with Huntington’s disease could not, proving they had learning and memory problems.

In a second study, both mouse groups had most of their whiskers trimmed on one side. After the intact whiskers were stimulated, the touch and sensation brain region increased in area in the normal mice, but not the Huntington’s disease mice. This showed that the Huntington’s diseased brain had lost its ability to change wiring patterns and suggests that the neurons were unable to reorganise themselves and strengthen their nerve connections. Humans with Huntington’s disease also have problems with touch perception.

While more research is needed, Dr Hannan noted that Alzheimer’s disease patients may also have defective nerve connections in the brain similar to Huntington’s disease. If this is true, it might be possible to develop anti-dementia drugs that enhance information processing for both disorders.

Dr Anthony Hannan and his team collaborated with researchers from Oxford University and Nencki Institute of Experimental Biology in Poland on the project. Their findings were reported in the March 23 edition of The Journal of Neuroscience.

The Howard Florey Institute is Australia’s leading brain research centre. Its scientists undertake clinical and applied research that can be developed into treatments to combat brain disorders, and into new medical practices. Their discoveries will improve the lives of those directly, and indirectly, affected by brain and mind disorders in Australia, and around the world. The Florey’s research areas cover a variety of brain and mind disorders including Parkinson’s disease, stroke, motor neuron disease, addiction, epilepsy, multiple sclerosis, muscular dystrophy, autism and dementia.

Merrin Rafferty | EurekAlert!
Further information:
http://www.hfi.unimelb.edu.au

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