ABOVE: Major workers (left) harbor higher levels of a hormone-degrading enzyme (green) in the blood-brain barrier than minor workers (right). Linyang Ju

Despite having identical genes, carpenter worker ants vary wildly in their behaviors and appearances. Major workers fight off predators and are bulkier than minor workers that gather food and tend to youngsters. These differences depend on the action of juvenile hormone (JH3), a crucial regulator of insect development.

The amount of JH3 that leaks into the brain is tightly controlled by the blood-brain barrier, a study published in Cell suggests. The findings point to the brain’s barrier as a contributor to key aspects of animal behavior.

A team led by biologist Shelley Berger of the University of Pennsylvania used single-cell RNA sequencing to compare gene expression in Florida carpenter ants. Compared to their foraging counterparts, major workers expressed higher levels of an enzyme that degrades JH3. That enzyme, juvenile hormone esterase (Jhe), is trapped inside perineurial glial cells, which form the insect equivalent of the blood-brain barrier. 

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When the researchers ratcheted up levels of the hormone either by injecting JH3 into the brain or by repressing the enzyme with siRNA, major ants neglected their soldierly duties in favor of foraging.  

These findings hint that the brain’s barrier, often downplayed as a passive membrane or an obstacle to treating neurological conditions, mediates the interaction between hormones and neurons, according to entomologist Naoki Yamanaka of the University of California, Riverside, who was not involved in the study. 3,4,5 “[It] changes our view of the blood-brain barrier.”

Juvenile hormones are present among all insects, and similar mechanisms may operate in other species, added Yamanaka. Indeed, when Berger’s team artificially expressed ant Jhe in the blood-brain barriers of Drosophila, the flies spent less time seeking out food. 

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“Ants provide this amazing system to help understand some of the determinants of behavior because of this remarkably stereotypic social structure,” said Berger. Now, her team is investigating whether the blood-brain barrier performs a similar role in mammals. 

Initial evidence suggests that it might. By scouring publicly available data, Berger and her colleagues found other hormone-degrading enzymes, including one that breaks down testosterone, in the mouse brain’s endothelial layer. This hints that the blood-brain barrier may regulate aspects of mammalian reproduction. “That’s pretty fascinating,” said Berger.