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Fat rat study parallels human results in how Type 2 Diabetes impairs memory


Trent-Baycrest research team confirms hippocampus is at greatest risk of damage in early stages of disease

November 9, 2005

Dr. Gordon Winocur(Peterborough, ON) – Canadian scientists studying overweight, insulin-resistant rats have found further evidence that the hippocampus, which controls important memory functions, is particularly susceptible to damage in the early stages of Type 2 Diabetes.

The findings by a team of researchers at Trent University (recently named Research University of the Year for the third year in a row) and Baycrest (a world-renowned healthcare and research facility for aging adults) are reported in the October 2005 issue of Behavioral Neuroscience, published by the American Psychological Association, and which has just come out. The results parallel those of human studies in pointing to the vulnerability of the hippocampus and related structures when Type 2 Diabetes strikes.

While there is growing evidence linking diabetes to cognitive complications in humans, scientists still don't understand what areas of the brain are most prone to malfunction in the presence of this diabetes, from early onset to advanced disease, and why this happens.

"What we're finding is that in the early stages of diabetes, the cognitive impairment is limited to memory function that is controlled by the hippocampus," says lead investigator Dr. Gordon Winocur, a Trent University Psychology professor, and senior scientist and vice-president of research with The Rotman Research Institute at Baycrest. The hippocampus, a seahorse-shaped area located on each side of the brain, plays an essential role in registering new memories and retrieving them.

"Memory loss of this nature is the first sign of dementia and it could be a precursor to vascular dementia or Alzheimer's disease".

An animal model affords researchers the opportunity to ask more questions and have greater latitude to look more closely at brain damage caused by diabetes by performing a post-mortem study of the rats' brains.

In this current study, researchers developed a rigorous animal testing model for investigating the relationship between impaired gluco-regulation and cognition. Obese and lean rats were put through a series of learning and memory recall exercises in a simple box environment outfitted with a single retractable level attached to a central feeder (or food reward). The obese rats had a genetic mutation causing insulin resistance that mimicked the human form of the early stages of Type 2 Diabetes.

The rats underwent go/no-go training to learn when to press the lever to receive food and when not to. During training, the two groups of rats did not differ in learning the rules and both scored well. However, in the actual trials that began a day after the training, and that tested their ability to remember what they'd learned, the differences in cognitive function began to show. This became particularly evident the longer the delay between trials.

The performance of the obese rats deteriorated significantly at longer inter-trial intervals that challenged their ability to recall specific information. This critical memory function is thought to be associated with the hippocampus.

Following the behavioural trials, the rat brains were sent to the University of South Carolina's School of Medicine for study. Collaborators there uncovered a specific receptor – GLUT4 – in the hippocampus that may malfunction with the onset of diabetes. GLUT4 is a protein that researchers believe is critical in helping brain cells to use glucose as a metabolic fuel, although how this interplay happens requires further research.

"One exciting aspect of our study is that our data suggest that deficits in insulin signaling and GLUT4 transfer in the hippocampus may contribute to the neurological complications of diabetes – that result in cognitive impairment," says Dr. Winocur.

"A combination of lifestyle changes and drugs" may be the key to reducing memory loss and delaying the onset of dementia in adults with diabetes, he adds.

In Canada, 60,000 new cases of Type 2 Diabetes are diagnosed each year, with another 25,000 people dying each year from diabetes-related complications, including cardiovascular disease and kidney disease. 

Dr. Winocur's collaborators on the study were Drs. Carol Greenwood, University of Toronto; Bruce McEwen, Rockefeller University; and Lawrence Reagan, Gerardo Piroli, Claudia Grillo and Leah Reznikov, all with the University of South Carolina.

The research was supported by Science and Engineering Research Canada, the Juvenile Diabetes Research Foundation International, the National Institute of Mental Health and other granting bodies.

Baycrest is an internationally-renowned academic health sciences centre that is advancing the care and quality of life of older adults through the power of research and education, with a focus on brain functioning and mental health. It is affiliated with the University of Toronto.

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For more information on this study, or to interview lead author Dr. Gordon Winocur, please contact:

Laura Copeland
Communications Officer
Trent University
705.748.1011, ext. 1456

Kelly Connelly
Senior Media Relations Officer


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Last Updated November 11, 2005