Summary: The blood-brain barrier (BBB) in carpenter ants does more than protect the brain—it actively shapes individual behavior within colonies.
Researchers report that the ant BBB produces a specialized form of Juvenile hormone esterase (Jhe), an enzyme that breaks down the hormone Juvenile Hormone III (JH3). By limiting JH3 entry into the brain, the BBB helps determine whether a worker ant adopts foraging behavior or remains inside the nest as a soldier.
Preliminary evidence suggests comparable processes may occur in other animals, including mice, indicating this form of hormonal gating by the BBB could have broader biological significance.
Key Facts:
- The carpenter ant BBB produces a Jhe enzyme that degrades the behavior-modulating hormone JH3.
- Differences in BBB Jhe levels correlate with worker roles: higher enzyme levels reduce brain JH3 and are linked to non-foraging soldier behavior, while lower levels permit more JH3 and correlate with foraging.
- Early comparative data show mouse BBB cells also express hormone-degrading enzymes, including ones that can break down testosterone, suggesting a possible conserved mechanism across species.
Source: Cell Press
Background: In many animals, the blood-brain barrier maintains brain homeostasis by regulating the passage of molecules between the brain and circulating fluids. New research published in the journal Cell reveals that in carpenter ants the BBB plays an active, instructive role in controlling social behavior by locally processing hormones.
“In these ants, the BBB produces a specialized version of Juvenile hormone esterase (Jhe) that degrades Juvenile Hormone (JH3),” says Karl Glastad, co-lead author, with Linyang Ju, in the lab of senior author Shelley Berger at the Perelman School of Medicine, University of Pennsylvania.
Unlike typical Jhe proteins that are secreted into hemolymph (insect blood), the form produced by the ant BBB is retained inside BBB cells. There it regulates how much JH3 reaches the brain of a worker ant, effectively gating a hormone known to promote foraging.
Social insect colonies rely on division of labor: worker castes perform different tasks such as foraging outside the nest or defending the nest as soldiers. The study shows that variation in the BBB-localized Jhe between castes produces differing brain levels of JH3, which contributes to those distinct behavioral roles.
The discovery highlights how expression of a single protein in a specific tissue can have large-scale effects on individual behavior and, by extension, on colony function. The researchers also found initial evidence that a similar hormonal gating role for the BBB may exist in mammals.
The team used single-cell RNA sequencing (scRNA-seq) to compare gene expression across brain cell types in forager and soldier ants. Their analysis revealed that the gene for Jhe was expressed specifically in BBB cells and that its expression differed markedly between the two castes. To test the behavioral consequences, they manipulated Jhe levels experimentally.
Lowering Jhe in soldiers caused increased brain JH3 and triggered foraging behavior, effectively reprogramming caste-specific behavior. Conversely, placing the ant Jhe into the blood-brain barrier of Drosophila—where fly Jhe is normally extracellular—reduced food-seeking behavior in flies, demonstrating a functional effect when the enzyme is localized to the BBB.
“Differences in BBB expression of this single enzyme control the crucial decision to forage or remain in the nest for defense,” Glastad explains. “Even flies can be reprogrammed to change food-seeking behavior when the ant Jhe is expressed in their BBB.”
To explore whether hormones are gated by the BBB in other animals, the researchers analyzed existing mouse endothelial cell data. They found several hormone-degrading enzymes enriched in mouse BBB cells compared with other endothelial types, notably enzymes that degrade testosterone.
“These results suggest hormone gating by the BBB may extend beyond ants,” says Berger. “Differential gating of hormones between behavioral states, as seen in ants, could be a broader biological strategy, including in mammals.”
The researchers plan future studies to trace the evolutionary origins and distribution of this mechanism, and to determine whether BBB-based hormonal regulation is a convergent strategy for shaping behavior across species.
Funding: This research was supported by the NIH and NSF.
About this neuroscience and behavior research news
Author: Kristopher Benke
Source: Cell Press
Contact: Kristopher Benke – Cell Press
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Hormonal gatekeeping via the blood brain barrier governs caste specific behavior in ants” by Karl Glastad et al., Cell. DOI: 10.1016/j.cell.2023.08.002
Abstract
Hormonal gatekeeping via the blood brain barrier governs caste specific behavior in ants
Highlights
- Single-cell RNA-seq identifies a hormone-degrading esterase (CfJhe) localized to the ant BBB.
- CfJhe expression is high in non-foraging major-worker BBB cells, producing lower brain JH3 levels.
- Heterologous expression of ant CfJhe in the fly BBB reduces foraging-like behavior.
- Knockdown of CfJhe in major workers induces acquisition of foraging behavior.
Summary
This study reveals an unexpected regulatory role for the blood-brain barrier in social behavior. Using single-cell transcriptomics, the investigators localized juvenile hormone esterase (Jhe) to the BBB and demonstrated that its activity determines how much juvenile hormone (JH3) reaches the brain. Manipulating Jhe levels reprograms the brain transcriptome and switches behavioral phenotypes between ant castes.
Although ant Jhe functions intracellularly within BBB cells, Drosophila Jhe is typically extracellular; yet expressing the ant Jhe in the fly BBB still altered behavior. Most strikingly, altering Jhe in ants reprograms complex caste-specific behaviors. These findings point to a potentially conserved role for the BBB as a molecular gatekeeper of neurohormonal pathways that control social behavior.