How can exercise protect against Alzheimer's disease?

NEW YORK, NY (February 8, 2019) – Athletes know that a vigorous workout can release a flood of endorphins: "wellness" hormones that improve mood. According to a study jointly conducted by Ottavio Arancio, MD, PhD, a researcher at the College of Physicians and Surgeons Vagelos of Columbia University, the exercise shows that another hormone can improve memory and protect against Alzheimer's disease. Alzheimer's disease and the aging brain.

The study was published in Nature Medicine.

Physical activity is known to improve memory and studies suggest that it could also reduce the risk of Alzheimer's disease. But researchers do not understand why.

A few years ago, practicing researchers discovered a hormone called irisine, which is released into the circulation during a physical activity. Early studies have suggested that irisine plays primarily a role in energy metabolism. But new research has shown that the hormone can also promote neuronal growth in the hippocampus of the brain, an area essential for learning and memory.

"This suggests the possibility that irisin may help explain why physical activity improves memory and appears to play a protective role in brain conditions such as Alzheimer's disease," says Arancio, Professor of Pathology and Cell Biology and Medicine at Columbia University of Vagelos College. doctors and surgeons.

In this new study, Arancio and his colleagues at the Federal University of Rio de Janeiro in Brazil and Queens University of Canada began by looking for a link between irisin and Alzheimer's disease in humans. Using tissue samples taken from brain stores, they discovered that irisin was present in the human hippocampus and that hormone levels in the The hippocampus was reduced in people with Alzheimer's disease.

To explore what irisin does in the brain, the team has turned to the mouse. These experiments show that irisin, in mice, protects brain synapses and animal memory: when irisine is turned off in the hippocampus of healthy mice, synapses and memory are weakened. Similarly, increasing levels of irisin in the brain has improved both measures of brain health.

The researchers then examined the effect of exercise on irisin and the brain. As part of the most compelling experiments in the study, researchers found that mice swimming almost daily for five weeks did not exhibit memory impairment despite beta-amyloid infusions – the neuron-destroying protein involved in Alzheimer's disease.

By blocking irisin with a drug, the researchers also discovered that the benefits of swimming were totally eliminated. Mice that swam and were treated with irisin-blocking substances did not behave better in memory tests than sedentary animals after beta-amyloid infusions.

Together, the results suggest that irisine could be harnessed to find a new treatment to prevent or treat dementia in humans, says Arancio. His team is now researching pharmaceutical compounds that can increase brain levels of the hormone or mimic its action.

"In the meantime, I would certainly encourage everyone to exercise, to promote brain function and health in general," he said. "But this is not possible for many people, especially those with aging-related conditions such as heart disease, arthritis or dementia." For these people, there is a need particular drugs that mimic the effects of irisin, protect synapses and prevent cognitive decline. "

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The study called "FNDC5 / irisin, linked to exercise, saves synaptic plasticity and memory defects in Alzheimer's models". The other contributors are: Mychael V. Lourenco (Federal University of Rio de Janeiro, Rio de Janeiro, Brazil and CUIMC); Rudimar L. Frozza (Federal University of Rio de Janeiro and Oswaldo Cruz Institute, Oswaldo Cruz Foundation, FIOCRUZ, Rio de Janeiro); Guilherme B. de Freita (Federal University of Rio de Janeiro and Queen's University, Kingston, Ontario, Canada); Hong Zhang (CUIMC); Grasielle C. Kincheski (Federal University of Rio de Janeiro); Felipe C. Ribeiro (Federal University of Rio de Janeiro); Rafaella A. Gonçalves (Queen's University, Kingston, Ontario, Canada); Julia R. Clarke (Federal University of Rio de Janeiro); Danielle Beckman (Federal University of Rio de Janeiro); Agnieszka Staniszewski (CUIMC); Hanna Berman (CUIMC); Lorena A. Guerra (Federal University of Rio de Janeiro); Letícia Forny-Germano (Federal University of Rio de Janeiro); Shelby Meier (University of Kentucky, Lexington, KY); Donna M. Wilbad (University of Kentucky); Jorge M. de Souza (Federal University of Rio de Janeiro); Soniza Alves-Leon (Federal University of Rio de Janeiro); Vania F. Prado (University of Western Ontario, London, Ontario, Canada); Marco A. M. Prado (University of Western Ontario); Jose F. Abisambra (University of Kentucky); Fernanda Tovar-Moll (Gold Institute for Research and Education, Rio de Janeiro, Brazil and Federal University of Rio de Janeiro); Paulo Mattos (Gold Institute for Research and Education and Federal University of Rio de Janeiro); Sergio T. Ferreira (Federal University of Rio de Janeiro); and Fernanda G. De Felice (Federal University of Rio de Janeiro and Queen's University).

This work was funded by grants from the Alzheimer Society of Canada, the Weston Brain Institute (FGDF), the National Institute of Translational Neuroscience (NINT / Brazil), the Human Frontier Science Program, the International Society of Neurochemistry, National Institutes of Health (R01NS049442). Canadian Institutes of Health Research and Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação Carlos Chagas, member of the Foundation for the Treatment of the State of Rio de Janeiro.

The authors do not declare any conflict of financial or other interests.

The Irving Medical Center at Columbia University provides international leadership in the areas of basic, preclinical and clinical research; teaching of medical and health sciences; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists and nurses from the College of Physicians and Surgeons Vagelos, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and related research centers and institutions. The Irving Medical Center at Columbia University is home to the largest medical research enterprise in the city and state of New York and one of the Northeast's largest faculty clinics. For more information, visit cumc.columbia.edu or columbiadoctors.org.

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