Researchers at Michigan Medicine have found that a high-fat diet promotes an early inflammatory response in the mouse brain through immune pathways linked to diabetes and neurological disease, a potential bridge between metabolic dysfunction and cognitive impairment. suggesting sexuality.
For this study, The forefront of immunology, investigators analyzed the activation of the cGAS/STING immune pathway in a high-fat diet mouse model of prediabetes and cognitive impairment or dementia. Although no early changes in cognition were detected, results revealed insulin resistance and inflammatory activation of cGAS/STING and brain immune cells, microglia, within 3 days of feeding.
“Although there is evidence suggesting a role for cGAS/STING in obesity and diabetes, both of which predispose patients to cognitive impairment and dementia, the role of cGAS/STING in the brain has not been studied before. said Dr. Sarah Elzinga. She is the lead author and postdoctoral fellow in Michigan Medicine’s NeuroNetwork for Emerging Therapies.
“We found that this pathway is involved in the initial burst of microglia’s immune response, which plays an important role in Alzheimer’s disease and related dementias. Microglia are activated in the hippocampus under high-fat diet conditions.” This in turn can lead to inflammation and degeneration of the nervous system, and ultimately to cognitive impairment and dementia.”
Obesity and diabetes are highly associated with the development of dementia and other neurological disorders. Elzinga and the research team are investigating whether inhibiting the cGAS/STING pathway is a possible therapeutic target for reversing or preventing harmful changes in the brain in people who have developed cognitive impairment or dementia. , stated that further research is needed.
“Innovative ideas that could lead to new treatment paradigms are important in the fight against Alzheimer’s disease,” said senior author Eva Feldman, MD, Ph.D., James W. Albers Distinguished Professor at UM, Russell. N. DeJong Professor of Neurology said: Michigan He is also head of Medicine’s emerging therapeutics NeuroNetworks. “This study using cGAS/STING is her one such innovation and opens the door to exciting new therapeutic possibilities.”
Other authors include Dr. Rosemary Heng, Dr. Benjamin J. Murdoch, Dr. Bumsu Kim, John M. Hayes, Ian Weber Davis, Sam Teener, Krystal Pakat, Stephen I. Lenz, Ph.D., All About Michigan Medicine, Faye Medelson
Funding for this study was provided in part by the NIH National Institute of Diabetes and Peptic Kidney Disease and the National Institute on Aging.
Papers cited: “cGAS/STING after an acute high-fat diet and congenital cerebral inflammation” The forefront of immunology. DOI: 10.3389/fimmu.2022.1012594