PHILADELPHIA— The blood-brain barrier (BBB) has been found to play a significant role in controlling behavior critical to how ant colonies function, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The implications of this research on the intricate mechanisms behind ant behavior go beyond the world of ants. The findings, published this week in Cell, hint at similar mechanisms at play in other species, including mammals.
In ants, along with other animals, the BBB consists of tightly locked cells that protect the brain from germs and other harmful substances. The protective barrier plays a key role in how the brain and nervous system operate. The research, led by Shelley Berger, PhD, the Daniel S. Och University Professor and director of the Penn Epigenetics Institute, and her lab, focused on Carpenter ants and their unique caste-based behaviors. These different castes (social groups) within an ant colony often perform different tasks within the colony, and also often display drastic differences in lifespan.
In these ants, the BBB produces a specialized version of the enzyme Juvenile hormone esterase (Jhe), responsible for breaking down the Juvenile Hormone (JH3)—which regulates development and reproduction maturation. This Jhe enzyme is typically then deposited in the blood of the insect. However, the researchers found the Jhe enzyme produced by the BBB of carpenter ants is retained within the BBB cells. This localized enzyme controls the amount of JH3 that enters the brain of worker ants.
Different types of worker ants within the same colony have different responsibilities—such as gathering food, building tunnels, or defending the colony. The new findings show that this results, in part, from different levels of the JH3 enzyme expression in their BBB, leading to different levels of the hormone JH3 in the brain. These differences drive the diverse behaviors exhibited by different worker ants within the same colony, including foraging and defense.
“This research reveals a remarkable link between a single enzyme and complex social behaviors in ants,” said Berger. “A single enzyme can trigger a shift between distinct worker behaviors crucial for the colony's function. The blood-brain barrier's role in controlling these behaviors is truly remarkable and has implications beyond the ant world.”
The research began with single-cell RNA sequencing of different ant castes' brains—foragers and soldiers. This then revealed the distinct expression of the Jhe gene within the BBB cells. This finding, coupled with caste-specific differences, sparked the researchers' curiosity to unravel the broader implications of this mechanism in ant behavior.
“One surprising aspect of the study was the observation that manipulating Jhe levels in soldier ants led to a shift in behavior towards foraging,” said co-lead author Karl Glastad, PhD, a research associate in the Berger Lab. “This suggests that a single gene, encoding the Jhe enzyme, can substantially influence foraging behavior—a fundamental aspect of ant colony structure.”
The researchers also found that in Drosophila fruit flies the Jhe enzyme is naturally outside of cells. When they made the fly BBB express the ant version of the Jhe enzyme, they saw behavioral changes similar to those observed in the ants.
To see if similar mechanisms apply in other animals, the researchers also analyzed published data from a panel of mouse cells. The study's analysis of mouse endothelial cells suggests that BBB-controlled hormone entry into the brain might be a widespread phenomenon in the animal kingdom.
“This study showcases the power of modern biology techniques, such as single-cell sequencing, in uncovering hidden regulatory pathways,” said co-lead author Linyang Ju, a PhD candidate in the Berger Lab.
The researchers believe that this breakthrough could pave the way for understanding behavioral control in diverse organisms. Berger and her team are now focused on understanding the prevalence of this mechanism in other ant species and exploring its potential implications for behavior regulation in non-insect species.
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