Study Findings Suggest New Approaches to Treat Alzheimer’s and Other Neurodegenerative Diseases – ScienceDaily

This study in mice found that gut bacteria influence the behavior of immune cells throughout the body by producing compounds such as short-chain fatty acids. as Alzheimer’s disease. Findings published in the journal on January 13 chemistryopens up the possibility of reshaping the gut microbiota as a way to prevent or treat neurodegeneration.

“After just one week of antibiotics in young mice, we saw permanent changes in the gut microbiome, immune response, and the degree of neurodegeneration associated with a protein called tau experienced with age,” he said. Author David M. Holtzman says: MD, Barbara Burton and Reuben M. Morris III Distinguished Professor of Neurology. “What’s interesting is that by manipulating the gut microbiome, we can affect the brain without putting anything directly into it.”

Evidence is accumulating that the gut microbiota of patients with Alzheimer’s disease may differ from those of healthy individuals. It is not clear how changes in

To determine whether the gut microbiome may have a causative role, researchers altered the gut microbiota in mice prone to develop Alzheimer’s-like brain damage and cognitive deficits. Did. Mice have been genetically engineered to express a mutant form of the human brain protein tau, which accumulates and damages neurons by 9 months of age, causing brain atrophy.They also carried human variants appointment gene, the major genetic risk factor for Alzheimer’s disease.who has one copy of APOE4 Variants are 3-4 times more likely to develop the disease than more common people APOE3Mutant.

Along with Holzmann, the research team includes gut microbiome experts and co-authors Jeffrey I. Gordon, MD, and Robert J. Glazer, MD, directors of the Edison Family Center for Genome Science and Systems Biology. I was. Dr. Dong-Oh Seo, First Author, Neurology Instructor. Co-author Sangram S. Sisodia, Ph.D., is professor of neurobiology at the University of Chicago.

Such transgenic mice do not acquire a gut microbiota when housed in germ-free conditions from birth, and brain damage at 40 weeks of age is more pronounced than that of mice with normal mouse microbiota. was also shown to be much lower.

When such mice were housed under normal non-sterile conditions, they developed a normal microbiome. However, administration of antibiotics at 2 weeks of age permanently altered the composition of bacteria within the microbiome. The amount of overt brain damage was also reduced in male mice at 40 weeks of age. The protective effect of microbiome alterations was more pronounced in virus-carrying male mice. APOE3 Variants over high-risk individuals APOE4variant, possibly due to the detrimental effects of APOE4Some of the protections have been revoked, researchers say. Antibiotic treatment had no significant effect on neurodegeneration in female mice.

“We already know from studies of brain tumors, normal brain development, and related topics that immune cells in male and female brains respond very differently to stimulation,” Holtzman said. “Thus, it’s not too surprising that we found gender differences in responses when manipulating the microbiome, but what exactly does this mean for men and women living with Alzheimer’s disease and related disorders?” is difficult.

Further experiments revealed that three specific short-chain fatty acids, compounds produced as metabolites by certain types of gut bacteria, were associated with neurodegeneration. All three of these fatty acids were deficient in mice with altered gut microbiota by antibiotic treatment and were undetectable in mice without gut microbiota.

These short-chain fatty acids caused neurodegeneration by activating immune cells in the bloodstream, which somehow appeared to activate immune cells in the brain to damage brain tissue. When middle-aged mice with no microbiome were given three short-chain fatty acids, immune cells in the brain became more responsive and the brain showed more signs of tau-related damage.

“This study may provide important insights into how the microbiome influences tau-mediated neurodegeneration, and that therapeutics that alter the gut microbiome influence the development or progression of neurodegenerative diseases.” ,” said Linda McGovern, Ph.D., program director of the National Institute of Neurological Disorders and Stroke (NINDS), which provided some of the research funding.

This finding suggests new approaches to prevent and treat neurodegenerative diseases by altering the gut microbiota with antibiotics, probiotics, specialized diets, or other means.

“What I would like to know is that if we take a mouse that is genetically destined to develop a neurodegenerative disease and manipulate the microbiome just before the animal begins to show signs of damage, we can slow or prevent neurodegeneration. Holzmann asked, “This is the equivalent of starting treatment in a late middle-aged person who is cognitively normal but is failing. Neurodegeneration is the first manifestation.” If we can start treatment in these types of genetically sensitized adult animal models before they become, and show that it worked, it could be something that we can test in people. I have.