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<p>Best known for their functions in the nervous system, neurotransmitters also play prominent roles in wound healing. The study analysed the spatiotemporal expression of acetylcholine, dopamine, gamma-aminobutyric acid, serotonin, and its metabolite, 5-hydroxyindoleacetic acid, in regenerating mouse ear pinna during normal healing and during enhanced regeneration induced by the epigenetic inhibitor zebularine and retinoic acid, using HPLC-MS/MS. In terms of time, acetylcholine, dopamine, and gamma-aminobutyric acid showed a gradual decrease during the acute phase on days 3 and 7 post-injury, while serotonin, after a sharp decline on day 3, increased markedly. Zebularine and retinoic acid reduced gamma-aminobutyric acid, acetylcholine, and serotonin in the acute phase. On day 42, over 4 weeks after drug administration and 3 weeks after wound closure, the epigenetic treatment resulted in an elevation in serotonin and a decline in acetylcholine. In spatial terms, the neurotransmitter responses showed similar trends in the wound vicinity and distal tissues, except for a significant increase in serotonin in the wound area and gamma-aminobutyric acid in distal tissues on days 7 and 3, respectively. Decoding the concerted tissue profiles of small-molecule neurotransmitters helps reveal their roles in wound healing and informs the design of regenerative therapies targeting neurotransmitter pathways.</p>

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Insights into small-molecule neurotransmitter levels and distribution during tissue regeneration in an ear pinna model in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Anfisa Ronda,
  • Rafał Płatek,
  • Paulina Słonimska,
  • Katarzyna Kozłowska-Tylingo,
  • Paweł Sachadyn

摘要

Best known for their functions in the nervous system, neurotransmitters also play prominent roles in wound healing. The study analysed the spatiotemporal expression of acetylcholine, dopamine, gamma-aminobutyric acid, serotonin, and its metabolite, 5-hydroxyindoleacetic acid, in regenerating mouse ear pinna during normal healing and during enhanced regeneration induced by the epigenetic inhibitor zebularine and retinoic acid, using HPLC-MS/MS. In terms of time, acetylcholine, dopamine, and gamma-aminobutyric acid showed a gradual decrease during the acute phase on days 3 and 7 post-injury, while serotonin, after a sharp decline on day 3, increased markedly. Zebularine and retinoic acid reduced gamma-aminobutyric acid, acetylcholine, and serotonin in the acute phase. On day 42, over 4 weeks after drug administration and 3 weeks after wound closure, the epigenetic treatment resulted in an elevation in serotonin and a decline in acetylcholine. In spatial terms, the neurotransmitter responses showed similar trends in the wound vicinity and distal tissues, except for a significant increase in serotonin in the wound area and gamma-aminobutyric acid in distal tissues on days 7 and 3, respectively. Decoding the concerted tissue profiles of small-molecule neurotransmitters helps reveal their roles in wound healing and informs the design of regenerative therapies targeting neurotransmitter pathways.