# Hydrogen sulfide as a potent predator-derived kairomone mediating fear-related responses in mice

**Authors:** Ana Catarina Lopes, Julien Brechbühl, Aurélie de Vallière, Noah Gilliand, Flavio Ferreira, Marie-Christine Broillet

PMC · DOI: 10.1038/s42003-025-08592-w · Communications Biology · 2025-08-01

## TL;DR

Hydrogen sulfide, a toxic gas, acts as a warning signal for mice to detect nearby predators, triggering fear responses through specific neurons.

## Contribution

This study identifies hydrogen sulfide as a predator-derived kairomone detected by mouse olfactory neurons.

## Key findings

- Hydrogen sulfide activates Grueneberg ganglion neurons via CNGA3 channels, triggering fear-related behaviors.
- GG neurons are biologically relevant for detecting H2S, linking it to predator-prey dynamics.
- H2S serves as a kairomone signaling danger from predator secretions.

## Abstract

Olfaction plays a critical role in survival across species, notably in threat detection. Volatile olfactory molecules signaling the presence of a danger in the environment share a specific chemical signature, particularly sulfur-containing moieties detected by the mouse olfactory Grueneberg ganglion (GG) neurons. Our study focuses on one of the most toxic air pollutant, hydrogen sulfide (H2S). We reveal here a novel facet of H2S which acts as a danger signal, a kairomone alerting the prey for the presence of nearby predators as H2S can originate from meat-eater secretions. H2S activates the cyclic nucleotide-gated channels (CNGA3) present on the sensory cilia of GG neurons. This direct channel opening lets calcium into the cells ensuring neuronal activation and signal transmission to specific brain regions associated with stress and fear-related behaviors. Moreover, using GG-axotomized mice, we demonstrate the biological relevance of GG neurons to detect H2S. These results give new insights into predator-prey dynamics and danger communication which is fundamental for the survival of the species.

Detection of hydrogen sulfide by the neurons of the olfactory Grueneberg ganglion sheds light on a new kairomonal role for this toxic gas in predator-prey dynamics and danger communication

## Linked entities

- **Proteins:** CNGA3 (cyclic nucleotide gated channel subunit alpha 3)
- **Chemicals:** hydrogen sulfide (PubChem CID 402), H2S (PubChem CID 402)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Fos (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14281] {aka D12Rfj1, c-fos, cFos}, Mpst (mercaptopyruvate sulfurtransferase) [NCBI Gene 246221] {aka 3MST, Mst}, Cnga3 (cyclic nucleotide gated channel alpha 3) [NCBI Gene 12790] {aka CNG-3, CNG3}, Cbs (cystathionine beta-synthase) [NCBI Gene 12411] {aka HIP4}, Pag1 (phosphoprotein associated with glycosphingolipid microdomains 1) [NCBI Gene 94212] {aka Cbp, F730007C19Rik, Pag}, Cth (cystathionine gamma lyase) [NCBI Gene 107869] {aka 0610010I13Rik, CGL, CSE, Cys3}, Omp (olfactory marker protein) [NCBI Gene 18378], Pde1a (phosphodiesterase 1A, calmodulin-dependent) [NCBI Gene 18573], Cnga2 (cyclic nucleotide gated channel alpha 2) [NCBI Gene 12789] {aka CNG2, Cnca, Cncg4, OCNC1}, Rps6 (ribosomal protein S6) [NCBI Gene 20104] {aka S6R}, Gpx6 (glutathione peroxidase 6) [NCBI Gene 75512] {aka 1700020G18Rik, Ry2d1, olfactory}
- **Diseases:** metabolic disorders (MESH:D008659), Crohn's disease (MESH:D003424), inflammation (MESH:D007249), death (MESH:D003643), hypothermia (MESH:D007035), anxiety (MESH:D001007), cardiovascular diseases (MESH:D002318), intestinal diseases (MESH:D007410), cytotoxic (MESH:D064420), colon cancer (MESH:D015179), neurodegenerative diseases (MESH:D019636), ulcerative colitis (MESH:D003093), gastrointestinal diseases (MESH:D005767), fear (MESH:C000719212)
- **Chemicals:** nitrogen (MESH:D009584), H2O (MESH:D014867), FITC (MESH:D016650), sulfate (MESH:D013431), disulfide (MESH:D004220), Triton X-100 (MESH:D017830), Fura-2AM (MESH:C049925), agar (MESH:D000362), CO2 (MESH:D002245), isoflurane (MESH:D007530), sulfur (MESH:D013455), paraformaldehyde (MESH:C003043), CO (MESH:D002248), KCl (MESH:D011189), CaCl2 (MESH:D002122), rhodamine 110 (MESH:C049025), H (MESH:D006859), EDTA (MESH:D004492), NaHCO3 (MESH:D017693), ATP (MESH:D000255), NaCl (MESH:D012965), Fura-2 (MESH:D016257), azide (MESH:D001386), NaHS (MESH:C025451), Calcium (MESH:D002118), 2-methyl-2-thiazoline (MESH:C025765), D-glucose (MESH:D005947), HEPES (MESH:D006531), sulfhydryl (MESH:D013438), IAA (MESH:D007460), 8-Bromoguanosine 3',5'-cyclic monophosphate (MESH:C016276), L-Cysteine (MESH:D003545), 2-sec-butyl-4,5-dihydrothiazole (MESH:C049351), HCl (MESH:D006851), 2-nitro-5-thiobenzoic acid (MESH:C011136), PAF (-), SO2 (MESH:D013458), gentamycin (MESH:D005839), NO2 (MESH:D009585), F-127 (MESH:C078661), MgCl2 (MESH:D015636), DAPI (MESH:C007293), NO (MESH:D009569), H2S (MESH:D006862), 5,5'-dithio-bis-(2-nitrobenzoic acid) (MESH:D004228), Corticosterone (MESH:D003345), calcium phosphate (MESH:C020243), TX100 (MESH:C551282), 3-isobutyl-1-methylxanthine (MESH:D015056), cyclic nucleotides (MESH:D009712), NaOH (MESH:D012972), TNB (MESH:D014302)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Puma concolor (puma, species) [taxon 9696], Canis lupus (gray wolf, species) [taxon 9612], Procyon lotor (northern raccoon, species) [taxon 9654], Bos taurus (bovine, species) [taxon 9913], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Homo sapiens (human, species) [taxon 9606], Vulpes vulpes (red fox, species) [taxon 9627], Mustela erminea (ermine, species) [taxon 36723], Mephitis mephitis (striped skunk, species) [taxon 30548], Escherichia coli (E. coli, species) [taxon 562]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985), 293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), HEK — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_M624)

## Full text

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## Figures

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## References

9 references — full list in the complete paper: https://tomesphere.com/paper/PMC12317040/full.md

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Source: https://tomesphere.com/paper/PMC12317040