Exercise can ‘clean up’ Alzheimer’s environment

Study shows exercise generates new neurons, improves cognition in mouse model.

A study by a Massachusetts General Hospital (MGH) research team finds that neurogenesis — inducing the production of new neurons — in the brain structure in which memories are encoded can improve cognitive function in a mouse model of Alzheimer’s disease. Their investigation shows that cognition can be blocked by the hostile inflammatory environment in the brains of patients with Alzheimer’s disease and that physical exercise can “clean up” that environment, allowing new nerve cells to survive and thrive and improving cognition in the Alzheimer’s mice.

“In our study we showed that exercise is one of the best ways to turn on neurogenesis and then, by figuring out the molecular and genetic events involved, we determined how to mimic the beneficial effects of exercise through gene therapy and pharmacological agents,” said Rudolph Tanzi, director of the Genetics and Aging Research Unit, vice chair of the Department of Neurology, and co-director of the Henry and Allison McCance Center for Brain Health at MGH. Tanzi is the senior author of the paper published in Science.

Lead author Se Hoon Choi of the Genetics and Aging Research Unit said, “While we do not yet have the means for safely achieving the same effects in patients, we determined the precise protein and gene targets for developing ways to do so in the future.”

Adult neurogenesis — production of new neurons after the embryonic and, in some animals, neonatal periods — takes place in the hippocampus and another brain structure called the striatum. While adult hippocampal neurogenesis is essential to learning and memory, how the process impacts neurodegenerative conditions like Alzheimer’s has not been well understood. The MGH team set out to investigate how impairment of adult hippocampal neurogenesis (AHN) contributed to Alzheimer’s pathology and cognitive function in a mouse model, and whether increasing AHN could reduce symptoms.

Their experiments showed that AHN could be induced in the model either by exercise or by treatment with drugs and gene therapy that promoted the birth of neural progenitor cells. Behavioral testing on animals revealed limited cognitive benefits in animals in which neurogenesis had been induced pharmacologically and genetically. But animals in which AHN was induced by exercise showed improved cognitive performance and reduced levels of beta-amyloid, the main component of plaques in Alzheimer’s brains.

“Although exercise-induced AHN improved cognition in Alzheimer’s mice by turning on neurogenesis, trying to achieve that result by using gene therapy and drugs did not help,” Tanzi said. “That was because newly born neurons, induced by drugs and gene therapy, were not able to survive in brain regions already ravaged by Alzheimer’s pathology, particularly neuroinflammation. So we asked how neurogenesis induced by exercise differs.”

Source:

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