The work, funded by Research into Ageing (Age UK) and the University and published in the Journal of Alzheimer’s Disease, may also explain why people who are susceptible to stress are at more risk of developing the disease.
Alzheimer’s disease is the most common cause of dementia affecting almost 500,000 people in the UK, the majority of who are over the age of 65. Symptoms can include memory loss, mood changes and problems with communicating and reasoning.
There is no cure for Alzheimer’s and, although there are a few treatments available that can reduce the symptoms in some people, they cannot halt the progression of the disease.
Increasingly, there is evidence that physical and mental activity can reduce people’s chances of developing the disease or can slow down it’s progression but up until now it has been unclear how this happens.
The Nottingham team, led by Dr Marie-Christine Pardon in the School of Biomedical Sciences, has discovered that the stress hormone CRF — or corticotrophin-releasing factor — may have a protective effect on the brain from the memory changes brought on by Alzheimer’s disease.
CRF is most associated with producing stress and is found in high levels in people experiencing some forms of anxiety and depressive diseases. Normal levels of CRF, however, are beneficial to the brain, keeping the mental faculties sharp and aiding the survival of nerve cells. Unsurprisingly then, studies have shown that people with Alzheimer’s disease have a reduced level of CRF.
The researchers used an experimental drug to prevent the hormone from binding to a brain receptor called CRFR1 in mice with Alzheimer’s disease that were free from memory impairments, therefore blocking the effects of the hormone. They discovered that the mice had an abnormal stress response with reduced anxiety but increased behavioural inhibition when confronted by a stressful situation — in this case being placed in a new environment — and this is was due to the abnormal functioning of the CRFR1. This abnormal stress response before the onset of symptoms may explain why people susceptible to stress are more at risk of developing Alzheimer’s.
Dr Pardon and her team also found that interrupting the hormone from binding on to the CRFR1 receptor blocked the improvement of memory normally promoted by exercise. However, in mice with Alzheimer’s a repeated regime of moderate exercise restored the normal function of the CRF system allowing its memory enhancing effects. The results are in line with the idea that regular exercise is a means of improving one’s ability to deal with everyday stress in addition to keeping mental abilities keen.
Finally, their study showed that the switching on of this particular brain receptor during exercise increased the density of synapses, which makes the connection between nerve cells, the loss of which is thought to be responsible for the early memory loss seen in Alzheimer’s patients.
Dr Pardon said: “This is the first time that researchers have been able to identify a brain process directly responsible for the beneficial effects of exercise in slowing down the progression of the early memory decline characteristics of Alzheimer’s disease.
“Overall, this research provides further evidence that a healthy lifestyle involving exercise slows down the risk of Alzheimer’s disease and opens avenues for the new interventions targeting the altered CRFR1 function associated with the early stages of the disease.”
An early online version of the paper — Corticotropin-Releasing Factor Receptor 1 Activation During Exposure to Novelty Stress Protects Against Alzheimer’s Disease-Like Cognitive Decline in AβPP/PS1 Mice — detailing the findings has been published online at http://iospress.metapress.com/content/75m787746365k55g/?p=8dd6b9cb0afd4f2ebc9937ffbc7fc985&pi=0
More information is available from Dr Marie-Christine Pardon on +44 (0)115 823 0149, [email protected] or Emma Thorne, Media Relations Manager in the Communications Office at The University of Nottingham, on +44 (0)115 951 5793, [email protected]
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Notes to editors:
Corticotropin-Releasing Factor Receptor 1 Activation During Exposure to Novelty Stress Protects Against Alzheimer’s Disease-Like Cognitive Decline in AβPP/PS1 Mice
Gillian A. Scullion, Katherine N. Hewitt and Marie-Christine Pardon
JAD Volume 34/Issue 3 (March 2013)
The Journal of Alzheimer’s Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer’s Disease has an Impact Factor of 3.745 according to Thomson Reuters’ 2011 Journal Citation Reports. It is ranked #22 on the Index Copernicus Top 100 Journal List. The Journal is published by IOS Press (www.iospress.com).
Notes to editors: The University of Nottinghamhas 42,000 students at award-winning campuses in the United Kingdom, China and Malaysia. It was ‘one of the first to embrace a truly international approach to higher education’, according to the Sunday Times University Guide 2013. It is also one of the most popular universities among graduate employers, one of the world’s greenest universities, and winner of the Times Higher Education Award for ‘Outstanding Contribution to Sustainable Development’. It is ranked in the UK’s Top 10 and the World’s Top 75 universities by the Shanghai Jiao Tong and the QS World Rankings.
More than 90 per cent of research at The University of Nottingham is of international quality, according to the most recent Research Assessment Exercise. The University aims to be recognised around the world for its signature contributions, especially in global food security, energy & sustainability, and health. The University won a Queen’s Anniversary Prize for Higher and Further Education for its research into global food security.