2. Academic Validation
  3. Serotonin promotes lip sensory recovery after inferior alveolar nerve transection via histone serotonylation

Serotonin promotes lip sensory recovery after inferior alveolar nerve transection via histone serotonylation

  • J Dent Sci. 2025 Oct;20(4):2363-2374. doi: 10.1016/j.jds.2025.04.001.
Suning Mao 1,  Gaowei Zhang 1 2,  Pingchuan Ma 1 2,  Zhongkai Ma 1 2,  Chunjie Li 1 2,  Li Ye 1 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 2 Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 3 Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
PMID: 41040553 DOI: 10.1016/j.jds.2025.04.001
Abstract

Background/purpose: Sensory impairment due to Inferior alveolar nerve injury in mandibular tumor ablation severely impairs the survivors' quality of life. This study explored the role of serotonin in lip sensory recovery after inferior alveolar nerve transection.

Materials and methods: We established an in vivo inferior alveolar nerve transection model using C57BL/6J mice and an in vitro model of primary neurons in trigeminal ganglia. Serotonin or Transglutaminase 2 inhibitor (GK921) were administrated to mice or neurons. The degree of lip sensory recovery was confirmed by quantitative sensory testing with Von Frey filaments. The axonal length was directly measured under optical microscopes. The changes of histone serotonylation and axon regeneration-related molecules were validated by quantitative real-time polymerase chain reaction, Western blot, immunofluorescence, and enzyme-linked immunosorbent assay.

Results: Lip sensory functions could recover without additional interventions within 4 weeks. Serotonin production, histone serotonylation, and Transglutaminase 2 were upregulated in the ipsilateral trigeminal ganglia. Exogenous serotonin could improve axon growth with histone serotonylation. Additional serotonin could slightly compress the lip sensory recovery time, and an increase in histone serotonylation and axon growth-related molecules were observed in the ipsilateral trigeminal ganglia. Oppositely, GK921 significantly reduced the axon length and delayed the lip sensory recovery after inferior alveolar nerve transection.

Conclusion: Serotonin could accelerate the lip sensory recovery after inferior alveolar nerve transection via increasing histone serotonylation. These results may offer a potential therapeutic approach for peripheral nerve injury and studies may be needed to validate the efficacy in Other peripheral nerve injury models.

Keywords

5-hydroxytryptamine; Axonal regeneration; Histone monoaminylation; Peripheral nerve injury; Trigeminal nerve.

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