# The impact of nicotine on the olfactory memory and its relationship with TRPA1

**Authors:** Kazuya Mizobata, Hideki Sakatani, Masamitsu Kono, Shizuya Saika, Akinori Akaike, Muneki Hotomi

PMC · DOI: 10.1016/j.isci.2026.114908 · iScience · 2026-02-07

## TL;DR

Nicotine improves mouse olfactory memory and protects brain cells through a receptor called TRPA1.

## Contribution

This study shows that nicotine's effect on olfactory memory depends on TRPA1 activation.

## Key findings

- Oral nicotine treatment improves olfactory memory in mice.
- Nicotine reduces neuronal apoptosis in the piriform cortex.
- TRPA1 knockout abolishes nicotine’s beneficial effect.

## Abstract

Olfactory disorders are related to cognitive decline, yet effective treatments remain limited. Cigarette smoke impairs olfaction, but one of its components, nicotine, can protect nerve cells in the central nervous system. Transient receptor potential ankyrin 1 (TRPA1) is expressed in central olfactory tract conduction and can be activated by nicotine. We therefore investigated whether nicotine influences olfaction through TRPA1. After inducing olfactory damage with methimazole, one of the following agents was then administered for 42 days to wild-type (WT) and TRPA1 knockout (TRPA1 KO) mice: phosphate-buffered saline, cigarette smoke extract, or nicotine. Olfactory behavioral testing and histological analyses were performed. In WT mice, intraoral nicotine improved olfactory memory and reduced neuronal apoptosis in the piriform cortex (PC). In TRPA1 KO mice, however, these effects of nicotine were abolished. Nicotine improved olfaction through TRPA1 in central olfactory tract conduction. Nicotine may thus represent a potential therapeutic strategy for olfactory impairment.

•Oral nicotine treatment improves olfactory memory in mice•Nicotine reduces neuronal apoptosis in the piriform cortex•TRPA1 knockout abolishes nicotine’s beneficial effect•Nicotine’s neuroprotective action in the piriform cortex is TRPA1-dependent

Oral nicotine treatment improves olfactory memory in mice

Nicotine reduces neuronal apoptosis in the piriform cortex

TRPA1 knockout abolishes nicotine’s beneficial effect

Nicotine’s neuroprotective action in the piriform cortex is TRPA1-dependent

Biological sciences; Neuroscience; Cell biology

## Linked entities

- **Genes:** TRPA1 (transient receptor potential cation channel subfamily A member 1) [NCBI Gene 8989]
- **Chemicals:** nicotine (PubChem CID 942), methimazole (PubChem CID 1349907)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Gpx6 (glutathione peroxidase 6) [NCBI Gene 75512] {aka 1700020G18Rik, Ry2d1, olfactory}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Cth (cystathionine gamma lyase) [NCBI Gene 107869] {aka 0610010I13Rik, CGL, CSE, Cys3}, Omp (olfactory marker protein) [NCBI Gene 18378], Mcl1 (myeloid cell leukemia sequence 1) [NCBI Gene 17210] {aka Gm52627, Mcl-1}, Trpa1 (transient receptor potential cation channel, subfamily A, member 1) [NCBI Gene 277328] {aka Anktm1, TRPA1b}, Ank1 (ankyrin 1, erythroid) [NCBI Gene 11733] {aka Ank-1, nb, pale}, Pcx (pyruvate carboxylase) [NCBI Gene 18563] {aka Pc, Pcb}
- **Diseases:** viral infections (MESH:D014777), cerebral hypoperfusion (MESH:D002547), sarcopenia (MESH:D055948), neurodegenerative diseases (MESH:D019636), Anxiety (MESH:D001007), impairment within the central nervous system (MESH:D002493), PC (MESH:D000303), neurotoxicity (MESH:D020258), addiction (MESH:D019966), central disorders (MESH:D001304), ORN impairment (MESH:D060825), Alzheimer's disease (MESH:D000544), dysfunction of (MESH:D006331), loss of appetite (MESH:D001068), dementia (MESH:D003704), depression (MESH:D003866), hypoxia (MESH:D000860), OE (MESH:D000857), cognitive decline (MESH:D003072), sensorineural disorders (MESH:D006319)
- **Chemicals:** hematoxylin (MESH:D006416), phosphate (MESH:D010710), HE (MESH:D006371), saline (MESH:D012965), paraffin (MESH:D010232), Decalcifying Solution B (-), Nicotine (MESH:D009538), methylcyclopentenolone (MESH:C471838), HC-030031 (MESH:C552888), 2,4,5-trimethylthiazole (MESH:C424603), paraformaldehyde (MESH:C003043), beta-phenylethyl alcohol (MESH:D010626), Water (MESH:D014867), isovaleric acid (MESH:C008216), Methimazole (MESH:D008713), zinc sulfate (MESH:D019287), eosin (MESH:D004801)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Apis mellifera (bee, species) [taxon 7460], Nicotiana tabacum (American tobacco, species) [taxon 4097]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12936849/full.md

## References

72 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936849/full.md

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Source: https://tomesphere.com/paper/PMC12936849