They knew that chronic activation of the receptor Adora2a on the endothelial cells that line this important barrier in our brain can let factors from the blood enter the brain and affect the function of our neurons.
Now Medical College of Georgia scientists have shown that when they block Adora2a in a model of diet-induced obesity, this important barrier function is maintained.
Obesity - Insulin - Resistance - Blood - Brain
"We know that obesity and insulin resistance break down the blood brain barrier in humans and animal models, but exactly how has remained a mystery," says Dr. Alexis M. Stranahan, neuroscientist in the MCG Department of Neuroscience and Regenerative Medicine at Augusta University. Stranahan is corresponding author of the study published in The Journal of Neuroscience that provides new insight.
In the brain, adenosine is a neurotransmitter that helps us sleep and helps regulate our blood pressure; in the body it's also a component of the cell fuel adenosine triphosphate, or ATP. Adenosine also activates receptors Adora1a and Adora2a on endothelial cells, which normally supports healthy relationships between brain activity and blood flow.
Problems - Activation - Brain - Obesity - Stranahan
Problems arise with chronic activation, particularly in the brain, which is what happens with obesity, says Stranahan.
People who have obesity and diabetes have higher rates of cognitive impairment as they age and most of the related structural changes are in the hippocampus, a center of learning and memory and Stranahan's focus of study. Fat is a source of inflammation and there is evidence that reducing chronic inflammation in the brain helps prevent obesity-related memory loss.
Model - Mimics - Mice - Diet - Weeks
In a model that mimics what happens to some of us, young mice fed a high-fat diet got fat within two weeks, and by 16 weeks they had increases in fasting glucose and insulin concentrations, all signs that diabetes is in their future.
In the minute vasculature of the hippocampus, the investigators saw that obesity first...
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