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Rural Health
Spring 2017

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neurobiology

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Blood vessels in a mouse retina
 

A cellular trafficking system called transcytosis may do most of the work in controlling the permeability of the barrier between the blood and the central nervous system, according to research conducted in mice by neurobiologists at HMS.

The findings, published March 22 in Neuron by a team headed by Chenghua Gu, an HMS associate professor of neurobiology and senior author of the study, defy conventional scientific wisdom, which had held that zipperlike junctions between cells were responsible for closing off the barrier.

Barriers that keep our blood from diffusing into our brain, spinal cord, and retina evolved to prevent harmful substances from passing into the central nervous system from the bloodstream, yet this selectivity also blocks the passage of most medicines.

Most barrier investigations have focused on tight junctions. In recent years, however, Gu has called attention to the contributions of transcytosis, in which select molecules are transported across barrier cells in bubbles called vesicles.

Gu’s study revealed that, in mice, tight junctions in the retina are already in place at birth, when the blood-retinal barrier is still permeable, but that within about 10 days, the barrier gradually seals off completely, beginning in the center of the retina and moving outward.

“When we saw that the barrier was so leaky, we figured both tight junctions and transcytosis wouldn’t be formed yet,” Gu says.

The researchers found, however, that in the first days after birth, barrier cells hummed with vesicles ferrying molecules from the bloodstream to the retina. Yet by day 8, traffic had significantly slowed, and by day 10, it had crawled nearly to a halt. This plunge in transcytosis mirrored the pattern of barrier closure, spreading outward from the center of the retina.

If the findings are ultimately replicated in humans, whose blood-brain barrier forms before birth, they could lead to new avenues for opening the barrier to deliver drugs or tightening the barrier to treat retinal diseases and certain neurodegenerative diseases where barrier defects precede neuron death, including Alzheimer’s disease, ALS, and multiple sclerosis.

Image: Brian Chow

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Issue

Rural Health
Spring 2017

Topics

neurobiology

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