Tuesday, July 28, 2020
The Brain-Blood Filter?
A new study is changing the way we think about the so-called brain-blood
barrier. The study conducted by Stanford researchers and recently published in
the journal Nature demonstrates that hundreds of proteins that occur naturally
in healthy young mice's blood routinely enter into the mice's brains. While
previous research had shown almost no such permeability, these earlier studies
traced the passage into the brain of injected proteins that are naturally
absent or rare in the blood while the new research added fluorescent labels to
all of the hundreds of different proteins naturally occurring in mouse plasma.
The plasma proteins were then injected back into mice, and the researchers
looked for the proteins in the mice's brains. In young mice, about 2-3% of
those labeled proteins ended up in the brain. The proteins' entry was enabled
by specialized receptors found on the cells lining cerebral blood vessels while
a small amount of proteins leaked into the brain in a non-selective
manner. Interestingly, the selective receptor-driven form of
physiological uptake by the brain dwindled as the mice aged as did production
of the receptors required for their uptake. This previously unrecognized
age-associated change in how proteins are transported into the brain could have
clinical significance. For example, changes in protein trafficking to the
brain may result in mood and behavior changes and potentially underly
age-associated pathologies. Rather than thinking of it as the brain-blood
barrier it might be more helpful to think of it as a filter, one that can get
leaky or clogged as we age.
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I find it interesting that there is an age association of the permeability of plasma proteins through the BBB in these mice. I wonder if there is a similar correlation in humans as pertains to an age-related loss of receptors in the brain (i.e. dopaminergic) that would decay in the absence of any neurodegenerative disease such as Alzheimer's or PD. While these receptors are not directly within the BBB, a similar mechanism could be afoot. During my undergraduate years I worked under a PI, Dr. McFarland, who undertook extensive research in neurodegenerative diseases, specifically how such conditions lead to calcification in the basal ganglia and substantia nigra, as well as the formation of amyloid plaques in various regions of the brain (https://www.nature.com/articles/nn.2829). I would hypothesize that further research into the mice experiment could possibly show that there is age-related degenerative disease resulting in decay and possible calcification of receptors could be the culprit in the diminished number of receptors as age increases. That being said, the mice article references the BBB as a whole, and does not target specific anatomical sites in the cerebellum or cortex like the human neurodegenerative research does. So in the mice experiment, the pericytes in the membrane may be the targets of decay similar to how cells of the basal ganglia are targets of decay and calcification in aging humans.
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