Study shows how exercise generates new neurons, improves cognition in Alzheimer's mouse

September 6, 2018, Massachusetts General Hospital
Credit: CC0 Public Domain

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 those beneficial effects on cognition can be blocked by the hostile inflammatory environment present in the brain of patients with Alzheimer's disease and that physical exercise can "clean up" the environment, allowing new nerve cells to survive and thrive and improving cognition in the Alzheimer's mice.

"In our study we showed that 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 and pharmacological agents," says Rudolph Tanzi, Ph.D., director of the Genetics and Aging Research Unit, vice-chair of the Department of Neurology and co-director of the Henry and Alison McCance Center for Brain Health at MGH and senior author of the paper published in Science.

Lead author, Se Hoon Choi, Ph.D., of the Genetics and Aging Research Unit adds, "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 occurring 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 disease has not been well understood. The MGH team set out to investigate how impairment of adult hippocampal neurogenesis (AHN) contributed to Alzheimer's disease 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 of animals revealed limited cognitive benefits for 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.

"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 explains. "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."

Choi says, "We found the key difference was that exercise also turned on the production of brain-derived neurotrophic factor or BDNF—known to be important for the growth and survival of neurons—which created a more hospitable brain environment for the new neurons to survive. By combining drugs and gene therapy that both induced neurogenesis and increased BDNF production, we were able to successfully mimic the effects of exercise on cognitive function" Choi is an assistant professor of Neurology at Harvard Medical School (HMS).

Tanzi adds,"The lesson learned was that it is not enough just to turn on the birth of new nerve cells, you must simultaneously 'clean up' the neighborhood in which they are being born to make sure the new cells survive and thrive. Exercise can achieve that, but we found ways of mimicking those beneficial cognitive effects by the application of drugs and gene therapy that simultaneously turn on neurogenesis and BDNF production."

In another part of the study, the investigators found that blocking neurogenesis in young Alzheimer's mice shortly after birth led to more pronounced cognitive deficits later in life. "We will next explore whether safely promoting neurogenesis in Alzheimer's patients will help alleviate the symptoms of the disease and whether doing so in currently healthy individuals earlier in life can help prevent symptoms later on," says Tanzi, the Joseph P. and Rose F. Kennedy Professor of Neurology at HMS. "We are very excited to now investigate ways of implementing our new findings to more effectively treat and prevent this terrible disease."

Explore further: New neurons archive old memories

More information: "Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model" Science (2018). science.sciencemag.org/cgi/doi … 1126/science.aan8821

Related Stories

New neurons archive old memories

July 13, 2018
The ability to obtain new memories in adulthood may depend on neurogenesis—the generation of new neurons in the hippocampus—to clear out old memories that have been safely stored in the cortex, according to research in ...

Why BACE inhibitors may be failing Alzheimer's trials

July 30, 2018
Completely blocking the activity of an enzyme that produces amyloid plaques observed in Alzheimer's disease (AD) interferes with the regulation of new neurons generated in the adult hippocampus, according to a study of mice ...

Sustained aerobic exercise increases adult neurogenesis in the brain

February 8, 2016
It may be possible to increase the neuron reserve of the hippocampus – and thus improve preconditions for learning – by promoting neurogenesis via sustained aerobic exercise such as running

Alzheimer's risk gene impairs development of new neurons in mice

July 30, 2018
Scientists have taken a step closer to understanding how the strongest known genetic risk factor for Alzheimer's disease (AD) contributes to memory impairment. Reporting their findings in eNeuro, the researchers demonstrate ...

Serotonin mediates exercise-induced generation of new neurons

May 13, 2013
Mice that exercise in running wheels exhibit increased neurogenesis in the brain. Crucial to this process is serotonin signaling. These are the findings of a study by researchers at the Max Delbrück Center Berlin-Buch. Surprisingly, ...

Microfluidic system incorporates neuroinflammation into 'Alzheimer's in a dish' model

July 30, 2018
Building on their development of the first culture system to replicate fully the pathology behind Alzheimer's disease, a Massachusetts General Hospital (MGH) research team has now produced a system that includes neuroinflammation, ...

Recommended for you

Air pollution may be linked to heightened dementia risk

September 18, 2018
Air pollution may be linked to a heightened risk of developing dementia, finds a London-based observational study, published in the online journal BMJ Open. The associations found couldn't be explained by factors known to ...

A new approach for finding Alzheimer's treatments

September 11, 2018
Considering what little progress has been made finding drugs to treat Alzheimer's disease, Maikel Rheinstädter decided to come at the problem from a totally different angle—perhaps the solution lay not with the peptide ...

Study prevents cognitive decline in older blacks with memory loss

September 10, 2018
With nearly twice the rate of dementia as whites, blacks are at a higher risk for developing diseases like Alzheimer's, but there has been little research on how to reduce this racial health disparity. A new study in black ...

Excessive daytime sleepiness linked with brain protein involved in Alzheimer's disease

September 6, 2018
Analysis of data captured during a long-term study of aging adults shows that those who report being very sleepy during the day were nearly three times more likely than those who didn't to have brain deposits of beta amyloid, ...

Study shows how exercise generates new neurons, improves cognition in Alzheimer's mouse

September 6, 2018
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 ...

Novel strategy shows promise for earlier detection of Alzheimer's disease

September 4, 2018
Finding an effective way to identify people with mild cognitive impairment who are most likely to go on to develop Alzheimer's disease has eluded researchers for years. But now, a team of researchers led by David Loewenstein, ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

LaPortaMA
not rated yet Sep 08, 2018
One day all will know that the brain is NOT where memories are stored.
And that dementia is a matter of personal accountability.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.