Jul 18, 2019 | Updated: 10:03 AM EDT

Scientists Discovered How Obesity and Insulin Break Down Blood Brain-Barrier in Humans

Apr 22, 2019 08:01 AM EDT

Scientists Discovered How Obesity and Insulin Break Down Blood Brain-Barrier in Humans
(Photo : Phil Jones, Senior Photographer, Augusta University)

Scientists have reported that in humans, obesity can break down the protective blood barrier resulting in problems with learning and memory. Also, scientists know that chronic activation of the receptor Adora2a on the endothelial cells that line this essential barrier in the human brain can let factors from the blood enter the brain and disturb the performance of human neurons.

Scientists from Medical College of Georgia have now revealed that when they block Adora2a in a model of diet-induced obesity, there is sustenance in the function of this critical barrier.

As Dr. Alexis stated, they know that obesity and insulin resistance break down the blood-brain barrier in humans and animal models, but it remains a mystery exactly how this happens. Dr. Alexis M. Stranahan is a neuroscientist in the MCG Department of Neuroscience and Regenerative Medicine at Augusta University. The new insight provides in the study was published in the Journal of Neuroscience that Stranahan is the corresponding author.

Adenosine is a neurotransmitter that aids our sleep and helps regulate our blood pressure in the brain. In the body, it is also a component of the cell fuel adenosine triphosphate, or ATP. Adenosine also triggers receptors Adora1a and Adora2a on endothelial cells, which generally supports healthy relationships between brain activity and blood flow.

Stranahan emphasizes that with chronic activation, problems arise primarily in the brain which is what happens with obesity.

In a model related to what happens to humans, the researchers fed young mice with a high-fat diet and they got fat within two weeks, and by 16 weeks, they had excesses in fasting glucose and insulin concentrations, all signs that diabetes is in their future.

In the minute vasculature of the hippocampus, the researchers saw that obesity first increased the permeability of the blood-brain barrier to tiny molecules like fluorophore sodium fluorescein, Nafi. Insulin resistance that is diet-induced amplified that permeability so that a larger molecule, Evans Blue, which has a high affinity for serum albumin, the most abundant protein in the blood, also could get through.

Stranahan stressed that though it is typically hard to jump from mice to men, the fact that this type of work started with human findings likely means that avoiding insulin resistance could potentially halt the increased permeability of the blood barrier and decrease in cognitive function.

He said further that if a person has already progressed to insulin resistance, these studies underscore the essence of controlling blood sugar levels and avoiding advancing to insulin deficiency (diabetes), which opens the blood-brain barrier even further.

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