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A study conducted by a Massachusetts General Hospital research team reveals that neurogenesis (inducing the production of new neurons) in the brain structure where memories are encoded can improve cognitive function in a mouse model of Alzheimer's disease.
Their study shows that the hostile inflammatory environment present in the brain of Alzheimer's patients can block these beneficial effects on cognition and that physical exercise can cleanse the environment, allowing new nerve cells to survive and to improve. Alzheimer's mice.
"In our study, we showed that exercise is one of the best ways to activate neurogenesis. In determining the molecular and genetic events involved, we determined how to mimic the beneficial effects of exercise through gene therapy and pharmacological agents. Tanzi, director of the Genetics and Aging Research Unit and vice president of the department of neurology, said.
The paper was published in Science.
"Although we do not yet have the means to achieve the same effects safely in patients, we have determined specific protein and gene targets to be developed in the future," said Se Hoon Choi, of the Genetics and Aging Research Unit. .
Neurogenesis in the adult, or the production of new neurons occurring after the embryonic and, in some animals, neonatal periods, occurs in the hippocampus and in another brain structure called striatum. Although the neurogenesis of the hippocampus in adults is essential for learning and memory, its impact on neurodegenerative diseases such as Alzheimer's disease has not been well understood.
The team focused on studying how hippocampal neurogenesis in adults (AHN) contributes to the pathology and cognitive function of Alzheimer's disease and whether the increase in neurosis hematopoietic could reduce the symptoms.
Their experiments showed that AHN could be induced in the model either by exercise, or by treatment with drugs and gene therapy promoting the birth of neural progenitor cells. Behavioral tests in animals revealed limited cognitive benefits for animals where neurogenesis was induced pharmacologically and genetically. However, animals in which AHN was induced by exercise showed improved cognitive performance and reduced levels of beta-amyloid.
"Although exercise-induced AHN necrosis improves cognition in Alzheimer's mice by activating neurogenesis, trying to achieve this result by using gene therapy and drugs has not helped," said Tanzi. "Indeed, newborn neurons, induced by drugs and gene therapy, were not able to survive in brain regions already ravaged by Alzheimer's pathology, particularly neuroinflammation. We therefore asked how exercise-induced neurogenesis differs.
"We have discovered that the main difference lies in the fact that exercise has also resulted in the production of a neurotrophic factor derived from the brain or BDNF – known for its growth and survival – that creates a more cerebral environment. conducive to the survival of new neurons. By combining drugs and gene therapy both induced by neurogenesis and increased production of BDNF, we were able to mimic the effects of exercise on cognitive function, "said Choi.
"The teaching was that it is not enough to light the birth of new nerve cells, it must simultaneously" clean "the neighborhood in which they were born so that new cells survive and thrive. Exercise can do this, but we have found ways to mimic these beneficial cognitive effects through the application of drugs and gene therapies that simultaneously activate neurogenesis and BDNF production, "he added. Mr. Tanzi.
In another part of the study, researchers found that blocking neurogenesis in young Alzheimer's mice soon after birth resulted in more pronounced cognitive deficits later in life.
"We will then examine whether promoting neurogenesis safely in patients with Alzheimer's disease will help alleviate the symptoms of the disease and whether it can help prevent symptoms," concluded Tanzi. "We are very excited to now study ways to implement our new findings to more effectively treat and prevent this terrible disease."
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