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ARUK 2023 | Obesity and type 2 diabetes cause blood-brain barrier dysfunction and reduced brain blood flow

Fiona McLean, PhD, University of Dundee, Dundee, UK, shares insights from her research on the impact of obesity and type 2 diabetes (T2D) on the blood brain barrier (BBB). Using mouse models of obesity (60% high-fat diet) and T2D (leptin-receptor mutant mice), the team investigated brain blood vessel function using in vivo brain blood flow and oxygenated/deoxygenated hemoglobin imaging. In the obese mouse model, resting brain blood flow was reduced, but blood flow change in response to stimulus was unchanged. Whereas in the T2D model, resting blood flow and response in blood flow change to a stimulus were both decreased, as were oxygenated/deoxygenated hemoglobin levels. When investigating the potential molecular mechanisms driving these alterations, investigators noted reduced respiration, mitochondrial dysfunction, and changes in the expression of genes related to neurodegeneration. Ongoing efforts using single cell RNA sequencing will shed light on the links between metabolic disease and the BBB. This interview took place at the Alzheimer’s Research UK (ARUK) Conference 2023 in Aberdeen, UK.

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